Nitric oxide donor compounds

ABSTRACT

The invention relates to nitric oxide donor compounds and their use for treating cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolisms dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation, vascular diseases. The invention also relates to compositions comprising at least one nitric oxide releasing compounds of the invention and composition comprising at least one nitric oxide releasing compounds according to the invention and at least one 15 therapeutic agent.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No. 12/525,988, filed Nov. 17, 2009, which is a National Stage entry of International Application No. PCT/EP2008/051092, filed Jan. 30, 2008, which claims benefit of U.S. Provisional Application No. 60/899,422, filed Feb. 5, 2007. The disclosures of the prior applications are hereby incorporated in their entirety by reference.

The invention relates to nitric oxide donor compounds and their pharmaceutical compositions. The invention also relates to novel compositions comprising at least one nitric oxide releasing compounds and at least one therapeutic agent.

The invention also relates to the use of the nitric oxide donor compounds and their compositions for treating cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolism dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation, vascular diseases.

Nitric oxide (commonly referred to as NO) has been implicated in a wide range of biological functions. As a result, NO, and materials that release NO, are candidate therapeutics for a range of diverse disease states.

Nitric oxide donor compounds have been used for many years in the treatment of various clinical conditions, particularly coronary artery disease. The nitrovasodilators such as nitroglycerin (GTN) has been used for the treatment of various types of myocardial ischemia. Because of its pathogenic nature (chronicity with acute exacerbation), prophylactic and acute treatments are necessary to prevent complications with potentially fatal outcomes (>25% death for acute MI). Particularly the phenomenon of tolerance to the anti-anginal effects or GTN and to all other existing organic nitrates is of a special clinical significance. Early development of tolerance to the drug is by far the most serious drawback of nitrate therapy.

Other known methods of NO delivery include soluble, short-term NO donors, such as S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and incorporation of NO donors into polymeric matrices. In general, NO-nucleophile complexes (e.g., diazeniumdiolate ions) and NO-donating groups (e.g., S-nitrosothiols) may spontaneously decompose in aqueous environments, such as physiological or bodily fluids, to release NO. This rapid, spontaneous decomposition, however, may not be a favourable property for many therapeutic applications. Generally, a slower rate of decomposition and more steady evolution of NO are more efficacious.

Many of the existing NO donors must be administered intravenously, which results in rapid onset of decreasing blood pressure accompanied by unwanted side effects. Their effect does not extend beyond the period of infusion. Another undesirable side effect of some NO donors includes an increase in heart rate. A need exists for an NO donor compound to treat diseases that does not induce undesirable side effects.

The invention is directed to compounds that are particularly useful as nitric oxide donors having an improved pharmacological profile.

The invention provides compounds of the formula (I) and pharmaceutically acceptable salts or stereoisomers thereof

wherein:

-   s is 1; -   s′ and s″ are independently selected from 0 or 1, preferably s′ or     s″ is 1 or s′ and s″ are both 0; -   m, m′ and m″ are each independently selected from 0 or 1 with the     proviso that when m, m′ or m″ are 0, A is linked directly to the     groups —(Y—ONO₂), —(Y′—ONO₂), —(Y″—ONO₂), preferably at least one of     m, m′ or m″ is 1, or more preferably m, m′ and m″ are 0, -   B at each occurrence is independently selected from:

-   preferably B is

-   A is a radical selected from the group consisting of:

wherein:

-   in formulas (IIa)-(IIm) and (IIo)-(IIu), R₁ is selected from: -   H, —C(O)O—C(CH₃)₃, —C(O)—R_(1x), —C(O)O—R_(1x), wherein R_(1x) is     one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     reported; -   in formulas (IIa)-(IIu) R₂ is selected from: -   —C(O)OH, —C(O)—OC(CH₃)₃, —C(O)OR_(2x), —C(O)NHR_(2xx),     —C(O)N(CH₃)R_(2xx) where R_(2x) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     or 1, B is as above defined and Y, Y′ and Y″ are as below reported, -   R_(2xx) is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     reported, -   or R₂ is the group R₄:

-   in formula (IIa), R_(a) is selected from the groups consisting of: -   a) —H, —CH₃, isopropyl, isobutyl, sec-butyl, tert-butyl,     methylthio-(CH₂)₂—, phenyl, benzyl, C₆H₅—CH₂—CH₂—, 2-monosubstituted     benzyl, or 3-monosubstituted benzyl or 4-monosubstituted benzyl with     groups such as —F, —Cl, I, —NO₂, —CF₃, —CH₃, CN, C₆H₅CO—; -   or R_(a) is 2,4-dichlorobenzyl, 3,4-dichlorobenzyl,     3,4-difluorobenzyl, 3-triptophanyl-CH₂—, 3-benzothienyl-CH₂—,     4-imidazolyl-CH₂—, 9-anthranyl-CH₂—, cyclohexyl, cyclohexyl-CH₂—,     cyclohexyl-(CH₂)₂—, cyclopentyl-CH₂—, (C₆H₅)₂CH—, 4-quinolyl-CH₂—,     3-quinolyl-CH₂—, 2-quinolyl-CH₂—, 2-quinoxalyl-CH₂—, 2-furyl-CH₂—,     1-naphtyl-CH₂—, 2-naphtyl-CH₂—, 2-pyridyl-CH₂—, 3-pyridyl-CH₂—,     4-pyridyl-CH₂—, 2-thienyl-CH₂—, 3-thienyl-CH₂—, C₆H₄—CH═CH—CH₂—,     CH₂═CH—CH₂—, CH≡CH—CH₂—, NH₂—CO—CH₂—, NH₂—CO—(CH₂)₂—, or     —P(═O)(OCH₃)₂; -   b) HS—CH₂—, R_(bx)—C(O)—S—CH₂—, R_(bx)—OC(O)—S—CH₂—,     R_(bx)—NH—C(O)S—CH₂— wherein R_(bx) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-, 4-(R_(x)O)-3-nitrobenzyl- wherein     R_(x) is H, R_(xx)—C(O)—, R_(xx)—OC(O)—, R_(xx)—NHC(O)— wherein     R_(xx) is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     defined; -   d) R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂—, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is OH, (CH₃)₃CO—, R_(gx)—O—,     R_(gxx)—NH—, R_(gxx)—N(CH₃)— wherein R_(gx) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     or 1, B is as above defined and Y, Y′ and Y″ are as below reported,     R_(gxx) is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     reported, -   or R_(g) is the group R_(gg):

-   e) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an     integer from 0 to 4, R_(h) is H, (CH₃)₃C—OC(O)—, R_(hh)—C(O)— or     R_(hh)—OC(O)—, R_(i) is H, R_(ii)—C(O)— or R_(ii)—OC(O)—, wherein     R_(hh) and R_(ii) are each independently one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   in formula (IIc) R_(c) is selected from the following groups: -   a′) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     phenyl, benzyl, biphenyl-CH₂, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—; -   b′) HS—CH₂—, R_(bx)—C(O)—S—CH₂—, R_(bx)—OC(O)—S—CH₂—,     R_(bx)—NH—C(O)S—CH₂— wherein R_(bx) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   c′) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, R_(x)O—C₆H₄—CH₂— wherein R_(x) is     H, R_(xx)—C(O)—, R_(xx)—OC(O)—, R_(xx)—NHC(O)— wherein R_(xx) is one     of the groups —[(B)_(m)—(Y—ONO₂)]_(s), —[(B′)_(m′)—(Y′—ONO₂)]_(s′)     or —[(B″)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″     are 0 and Y, Y′ and Y″ are as below defined; -   d′) R_(g)C(O)CH₂—, R_(g)C(O)(CH₂)₂— wherein R_(g) is OH, (CH₃)₃CO—,     R_(gx)—O—, R_(gxx)—NH—, R_(gxx)—N(CH₃)— wherein R_(gx) is one of the     groups —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     or 1, and B is as above defined and Y, Y′ and Y″ are as below     reported, -   R_(gxx) is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     reported; -   e′) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an     integer from 0 to 4, R_(h) is H, (CH₃)₃C—OC(O)—, R_(hh)—C(O)— or     R_(hh)—OC(O)—, R_(i) is H, R_(ii)—C(O)— or R_(ii)—OC(O)—, wherein     R_(hh) and R_(ii) are each independently one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   in formula (IIf) Ph is phenyl, a′ is equal to 0, 1, 2, or 3, and a     is equal to 0 or 1 with the proviso that a is 0 or 1 when a′ is 0     and a is 0 when a′ is 1, 2 or 3; -   in formula (IIi) the group R₂ can be attached to one of the     positions 1, 2 or 3 of the cyclohexyl ring; -   in formulae (IIj) and (IIk) the symbol     represents a single bond or a double bond; -   in formula (IIk) the group R₂ can be attached to one of the     positions 1, 2 or 3 of the piperidyl ring; -   in formula (IIl), R_(L) is selected from: -   H, methyl, propyl, allyl, (C₆H₅)₂CH—, 1-naphthyl-CH₂—, benzyl,     2-bromobenzyl, 2-chlorobenzy, 3-chlorobenzyl, 4-fluorobenzyl,     4-bromobenzyl, 4-methylbenzyl; -   in formula (IIm) R_(m) is selected from: -   benzyl, 2-bromobenzyl, 4-bromobenzyl, 4-methylbenzyl; -   in formula (IIn) R_(n) is selected from: -   —H, —C(O)—R_(nx), —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h) wherein R_(h) is     —H, —C(O)O—C(CH₃)₃, —C(O)—R_(hh), —C(O)O—R_(hh) wherein R_(nx) and     R_(hh) are each independently one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   in formula (IIp), c is 0 or 1 and R₂ can be attached to the position     1, 2 or 3 of the phenyl ring; -   in formula (IIs), R₃ is selected from: -   OH, —OC(O)—R_(3x), —OC(O)O—R_(3x), —OC(O)—NH—R_(3x) wherein R_(3x)     is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula     I wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below defined; -   in formula (IIs) R_(s) is selected from the following groups: -   a″) —H, —CH₃, isopropyl, isobutyl, sec-butyl, tert-butyl,     methylthio-(CH₂)₂—, benzyl, 2-monosubstituted benzyl, or     3-monosubstituted benzyl, 3-triptophanyl-CH₂—, 4-imidazolyl-CH₂—,     NH₂—CO—CH₂—, NH₂—CO—(CH₂)₂—; -   b″) HS—CH₂—, R_(bx)—C(O)—S—CH₂—, R_(bx)—OC(O)—S—CH₂—,     R_(bx)—NH—C(O)S—CH₂— wherein R_(bx) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   c″) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-, 4-(R_(x)O)-3-nitrobenzyl- wherein     R_(x) is H, R_(xx)—C(O)—, R_(xx)—OC(O)—, R_(xx)—NHC(O)— wherein     R_(xx) is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     defined; -   d″) R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is OH, (CH₃)₃CO—, R_(gx)—O—,     R_(gxx)—NH—, R_(gxx)—N(CH₃)— wherein R_(gx) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s)—, [(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     or 1, B is as above defined and Y, Y′ and Y″ are as below reported,     R_(gxx) is one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),     —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of     formula (I) wherein m, m′ and m″ are 0 and Y, Y′ and Y″ are as below     reported, -   e″) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an     integer from 0 to 4, R_(h) is H, (CH₃)₃C—OC(O)—, R_(hh)—C(O)— or     R_(hh)—OC(O)—, R_(i) is H, R_(ii)—C(O)— or R_(ii)—OC(O)—, wherein     R_(hh) and R_(ii) are each independently one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   in formula (IIt) d is an integer from 2 to 5, d′ is 0 or 1, with the     proviso that d′ is 0 when d is an integer from 3 to 5, R_(t) is H,     —C(O)—R_(tt) or —C(O)O—R_(tt) wherein R_(tt) is one of the groups     —[(B)_(m)—(Y—ONO₂)]_(s), —[(B′)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B″)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are     0; -   in formula (IIu) a and b are each independently 0 or 1, R_(x) is H,     —C(O)—R_(xx), —C(O)O—R_(xx)—, —C(O)NH—R_(xx) wherein R_(xx) is one     of the groups —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or     —[(B)_(m″)—(Y″—ONO₂)]_(s″) of formula (I) wherein m, m′ and m″ are 0     and Y, Y′ and Y″ are as below defined; -   Y, Y′ and Y″ of the groups (Y—ONO₂), —(Y′—ONO₂) and —(Y″—ONO₂) of     formula (I) are bivalent radicals and they are each independently     selected from: -   A)     -   a straight or branched C₁-C₂₀ alkylene, preferably a straight or         branched C₂-C₁₀ alkylene     -   a straight or branched C₁-C₂₀ alkylene substituted with one or         more —ONO₂ group(s), preferably a straight or branched C₂-C₁₀         alkylene substituted with a —ONO₂ group;     -   a cycloalkylene having 5 to 7 carbon atoms, the ring being         optionally substituted with a straight or branched C₁-C₁₀ alkyl; -   B)

wherein n⁰ is an integer from 0 to 20, preferably n⁰ is from 0 to 5, more preferably n⁰ is 0 or 1,

-   n¹ is an integer from 1 to 20, preferably n¹ is an integer from 1 to     10, more preferably n¹ is an integer from 2 to 6; -   more preferably in formula (IB) and (IB′) n⁰ is 0 or 1 and n¹ is an     integer from 1 to 10;     wherein in formulas (IB) and (IB′) the —ONO₂ group is linked to     —(CH₂)_(n) ¹—; -   C)

wherein:

-   n¹ is an integer from 1 to 20, preferably n¹ is an integer from 1 to     10, or more preferably n¹ is an integer from 2 to 6, -   n² is an integer from 0 to 2, preferably n² is 1, -   R² is H or CH₃, preferably R² is CH₃, -   X₁ is —OC(O)— or —C(O)O—;     more preferably in formula (IC) n¹ is an integer from 1 to 10, n² is     1 and R² is CH₃, X₁ is —C(O)O—;     wherein in formula (IC) the —ONO₂ group is linked to —(CH₂)_(n) ¹—; -   D)

wherein in formula (ID):

-   n¹ is an integer from 1 to 20, preferably n¹ is an integer from 1 to     10, or more preferably n¹ is an integer from 2 to 10, -   n², R² and X₁ are as defined above; -   Y¹ is —CH₂—CH₂— or —CH₂═CH—(CH₂)_(n) ^(2a)— wherein n^(2a) is an     integer from 0 to 5, preferably n^(2a) is 0,     wherein in formula (ID) the —ONO₂ group is linked to —(CH₂)_(n) ¹—;     preferably in formula (ID), n² is 1 and R² is CH₃, Y¹ is     —CH═CH—(CH₂)_(n) ^(2a)— wherein n^(2a) is 0, X₁ is —C(O)O—, n¹ is an     integer from 1 to 10; -   E)

wherein X₂ is —O—, —S—, —NH— or —N(CH₂CH₂OCH₃)—, preferably X₂ is —O— or —NH—,

-   n³ is an integer from 1 to 5, preferably n³ is 1, -   n₃ is an integer from 0 to 10, preferably from 0 to 4, more     preferably n₃ is 0, -   n₄ an integer from 1 to 10, preferably from 1 to 4, more preferably     n₄ is 1 -   preferably n₃ is 0 and n₄ is 1; -   n_(3′) is an integer from 0 to 10, preferably n_(3′) is from 0 to 4, -   n_(4′) is an integer from 1 to 10, preferably from 1 to 4, -   more preferably n_(3′) is 0 and n_(4′) is 1, -   R² is H or —CH₃, preferably R² is H, -   preferably in (IE) n³ is an integer from 1 to 5, n₃ is 0 and n₄ is     from 1 to 4, n_(3′) is 0 and n_(4′) is from 1 to 4, R² is H and X₂     is —O— or —NH—, -   more preferably in (IE) n³ is 1, n³ is 0 and n₄ is 1, n_(3′) is 0     and n_(4′) is 1, R² is H and X₂ is —O— or —NH—,     wherein in formula (IE) the —ONO₂ group is linked to the     —(CH₂)_(n4′)— group; -   F)

wherein:

-   n⁵ is an integer from 0 to 10, preferably n⁵ is 0 or 1; -   n⁶ is an integer from 1 to 10, preferably n⁶ is 1; -   R⁴, R⁵, R⁶, R⁷ are the same or different, and are H or straight or     branched C₁-C₄ alkyl, preferably R⁴, R⁵, R⁶, R⁷ are H;     wherein in formula (IF) the —ONO₂ group is linked to

wherein n⁶ is as defined above;

-   Y² is an heterocyclic saturated, unsaturated, or aromatic 5 or 6     members ring, containing one or more heteroatoms selected from     nitrogen, oxygen, sulfur, -   and is selected from the group consisting of:

-   G)

wherein n⁰ is an integer from 0 to 10,

-   n⁷ is an integer from 1 to 10, preferably n⁷ is an integer from 1 to     6, more preferably n⁷ is 1; -   n⁸ is an integer from 0 to 10, preferably n⁸ is an integer from 0 to     6, more preferably n⁸ is 0; -   R⁸ is CH₃ or CH₂ONO₂, -   more preferably in formula (IG) n⁰ is 0, n⁷ is 1, n⁸ is 0 and R⁸ is     CH₃ or CH₂ONO₂,     wherein in formula (IG) the —ONO₂ group is linked to the group

-   preferably Y and Y′ or Y″ are equal; -   preferred (Y—ONO₂), —(Y′—ONO₂) or —(Y″—ONO₂) groups are:

-   more preferably the groups (Y—ONO₂), —(Y″—ONO₂), and —(Y″—ONO₂) are     each independently selected from:

-   with the proviso that in formula (I) s′ and s″ cannot be both 1     when:     -   A is the radical of formulas (IIb), (IId)-(IIr), or     -   A is the radical of formula (IIt) wherein d is from 3 to 5 and         d′ is 0, or     -   A is the radical of formula (IIu) wherein a is 0; -   with the proviso that s′ and s″ can be both 1 when:     -   A is the radical of formulas (IIa), (IIc) or (IIs) and R_(a),         R_(c) and R_(s) are selected from:         -   R_(bx)—C(O)—S—CH₂—, R_(bx)—OC(O)—S—CH₂—,             R_(bx)—NH—C(O)S—CH₂— wherein R_(bx) is one of the groups             —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or             —[(B)_(m″)—(Y″—ONO₂)]_(s″) wherein m, m′ and m″, B, Y, Y′             and Y″ are as above defined;         -   R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,             4-(R_(x)O)-3,5-diiodobenzyl, 4-(R_(x)O)-3-nitrobenzyl-             wherein R_(x) is R_(xx)—C(O)—, R_(xx)—OC(O)— or             R_(xx)—NHC(O)— wherein R_(xx) is one of the groups             —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′) or             —[(B)_(m″)—(Y″—ONO₂)]_(s″) wherein m, m′ and m″, B, Y, Y′             and Y″ are as above defined;         -   R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,             R_(g)C(O)(CH₂)₂—, wherein R_(g) is OH, (CH₃)₃CO—, R_(gx)—O—,             R_(gxx)—NH—, R_(gxx)—N(CH₃)— wherein R_(gx) and R_(gxx) are             one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),             —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″)             wherein m, m′ and m″, B, Y, Y′ and Y″ are as above defined;         -   R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an             integer from 0 to 4, R_(h) is R_(hh)—C(O)— or R_(hh)—OC(O)—,             R_(i) is R_(ii)—C(O)— or R_(ii)—OC(O)—, wherein R_(hh) and             R_(ii) are one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),             —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″)             wherein m, m′ and m″, B, Y, Y′ and Y″ are as above defined;     -   A is the radical of formula (IIt) wherein d′ is 1 and d is 2 and         R_(t) is —C(O)—R_(tt) or —C(O)O—R_(tt) wherein R_(tt) is one of         the groups —[(B)_(m)—(Y—ONO₂)]_(s), —[(B)_(m′)—(Y′—ONO₂)]_(s′)         or —[(B)_(m″)—(Y″—ONO₂)]_(s″) wherein m, m′ and m″, B, Y, Y′ and         Y″ are as above defined;     -   A is the radical of formula (IIu) wherein a is 1 and R_(x) is         —C(O)—R_(xx), —C(O)O—R_(xx)— or —C(O)NH—R_(xx) wherein R_(xx) is         one of the groups —[(B)_(m)—(Y—ONO₂)]_(s),         —[(B)_(m′)—(Y′—ONO₂)]_(s′) or —[(B)_(m″)—(Y″—ONO₂)]_(s″) of         formula (I) wherein m, m′ and m″, B, Y, Y′ and Y″ are as above         defined         with the proviso that the following compounds of formula (I) are         excluded: -   3-(nitrooxy)propyl 2-(tert-butoxycarbonylamino)-4-phenyl butanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate hydrochloride, -   4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-4-phenylbutanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate hydrochloride, -   (2-(nitrooxy)ethoxy)methyl     2-(tert-butoxycarbonylamino)-4-phenylbutanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate hydrochloride, -   1-tert-butyl 2-(4-(nitrooxy)butyl)pyrrolidine-1,2-dicarboxylate, -   4-(nitrooxy)butyl pyrrolidine-2-carboxylate hydrochloride, -   4-(nitrooxy)butyl pyrrolidine-2-carboxylate hydrochloride, -   1-tert-butyl 2-(3-(nitrooxy)propyl)pyrrolidine-1,2-dicarboxylate, -   3-(nitrooxy)propyl pyrrolidine-2-carboxylate, -   3-(nitrooxy)propyl pyrrolidine-2-carboxylate hydrochloride,

Another embodiment relates to compounds of formula (I)

wherein s is 1 and m is 0, s′ and s″ are 0,

-   A is selected from:

wherein

-   R₁ is H or —C(O)—OC(CH₃)₃, -   R₂ is —C(O)OR_(2x), —C(O)NHR_(2x), —C(O)N(CH₃)R_(2x) and more     preferably R₂ is —C(O)OR_(2x) or —C(O)NHR_(2x), wherein R_(2x) is     (Y—ONO₂) of formula (I) wherein Y is below reported, -   R_(a) of formula (IIa) is selected from: -   a) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     benzyl, C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—, 4-imidazolyl-CH₂—; -   b) HS—CH₂—, -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is H, -   d) R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, wherein R_(g) is OH, (CH₃)₃CO—,     or the group R_(gg):

-   e) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an     integer equal to 3 or 4, R_(h) is H or (CH₃)₃C—OC(O)—, R_(i) is H; -   R_(c) of formula (IIc) is selected from the group comprising: -   H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—, benzyl,     3-triptophanyl-CH₂, 4-imidazolyl-CH₂—, NH₂—CO—CH₂—, NH₂—CO—(CH₂)₂—; -   R_(L) of formula (IIl) is H, -   Y of the group (Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   B)

wherein in formula (IB)

-   n⁰ is from 0 to 5 and n¹ is an integer from 1 to 10; -   C)

wherein in formula (IC)

-   n¹ is an integer from 1 to 10, -   n² is 1 and R² is CH₃, X₁ is —C(O)O—; -   D)

wherein in formula (ID):

-   n² is 1 and R² is CH₃, -   Y¹ is —CH═CH—(CH₂)_(n) ^(2a)— wherein n^(2a) is 0, -   X₁ is —C(O)O— and n¹ is an integer from 1 to 10; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably the group —(Y—ONO₂) is selected from:

the following are preferred compounds according to the present invention:

Another embodiment provides compounds of formula (I)

wherein s and m are 1,

-   s′ and s″ are 0, -   B is selected from:

-   more preferably B is

-   A is a radical selected from:

wherein

-   R₁ is H or —C(O)O—C(CH₃)₃, -   R₂ is —C(O)OR_(2x) wherein R_(2x) is the group —[(B)—(Y—ONO₂)] of     formula (I) wherein B is as above defined and Y is below defined, -   R_(a) of formula (IIa) is selected from: -   a) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     benzyl, C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—, 4-imidazolyl-CH₂—; -   b) HS—CH₂—; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)— or (R_(x)O)-p-C₆H₄—CH₂—, wherein     R_(x) is H; -   d) R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, wherein R_(g) is OH or     (CH₃)₃C—O—, or the group R_(gg):

-   e) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃— wherein p is an     integer equal to 3 or 4, R_(h) is H or (CH₃)₃C—OC(O)—, R_(i) is H; -   R_(L) of formula (IIl) is H; -   Y of the group —(Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene,     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5 -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H;     preferably —(Y—ONO₂) is selected from:

The following are preferred compounds according to the present invention:

Another embodiment relates to compounds of formula (I)

wherein s is 1 and m is 0,

-   s′ and s″ are 0, -   A is a radical selected from

wherein is R₁ is —C(O)R_(1x), —C(O)OR_(1x) wherein R_(1x) is the group —(Y—ONO₂) of formula (I) wherein Y is below reported,

-   R₂ in formulas (IIa) (IIc) and (IIl) is —C(O)OH, —C(O)—OC(CH₃)₃ or     R₂ is the group R₄:

-   R₃ in formula (IIs) is OH; -   R_(a) of formula (IIa) is selected from: -   a) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     benzyl, C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—, 4-imidazolyl-CH₂—; -   b) HS—CH₂—; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂— wherein R_(x)     is H; -   d) R_(g)C(O)CH₂ or R_(g)C(O)(CH₂)₂—, wherein R_(g) is OH or     (CH₃)₃C—O—, or R_(g) is the group R_(gg):

-   e) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH(CH₂)₃—, wherein p is an     integer equal to 3 or 4, R_(h) is H or (CH₃)₃C—OC(O)—, R_(i) is H; -   R_(c) of formula (IIc) is selected from: -   H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—, benzyl,     3-triptophanyl-CH₂—, 4-imidazolyl-CH₂—, NH₂—CO—CH₂—, NH₂—CO—(CH₂)₂—; -   R_(L) of formula (IIl) is H; -   R_(s) of formula (IIs) is H, CH₃, isopropyl, isobutyl, sec-butyl,     methylthio-(CH₂)₂—, benzyl, 3-triptophanyl-CH₂—, 4-imidazolyl-CH₂—,     NH₂—CO—CH₂—, NH₂—CO—(CH₂)₂—; -   Y of the groups (Y—ONO₂ is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   B)

wherein in formula (IB)

-   n⁰ is from 0 to 5 and n¹ is an integer from 1 to 10; -   C)

wherein in formula (IC)

-   n¹ is an integer from 1 to 10, -   n² is 1 and R² is CH₃, X₁ is —C(O)O—; -   D)

wherein in formula (ID):

-   n² is 1 and R² is CH₃, -   Y¹ is —CH═CH—(CH₂)_(n) ^(2a) wherein n^(2a) is 0, -   X₁ is —C(O)O— and n¹ is an integer from 1 to 10; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably —(Y—ONO₂) is selected from:

the following are preferred compounds according to the present invention:

Another embodiment relates to compounds of formula (I)

wherein s and s′ are 1 and m, m′ are 0,

-   s″ is 0, -   A is a radical of formula (IIa)

wherein R₁ is —C(O)R_(1x), or —C(O)OR_(1x) wherein R_(1x) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below reported,

-   R₂ is —C(O)OH, —C(O)—OC(CH₃)₃ or R₂ is the group R₄:

-   R_(a) is selected from: -   b) R_(bx)C(O)—S—CH₂—, R_(bx)—OC(O)—S—CH₂—, R_(bx)—NH—C(O)S—CH₂—     wherein R_(bx) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂); -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is R_(xx)C(O)—, R_(xx)OC(O)— or R_(xx)NHC(O)— wherein R_(xx) is one     of the groups —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and     Y′ are below defined; -   d) R_(g)C(O)CH₂—, R_(g)C(O)(CH₂)₂—, wherein R_(g) is R_(gx)—O—,     R_(gxx)—NH—, wherein R_(gx) and R_(gxx) are one of the groups     —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below     defined; -   e) R_(h)NH(CH₂)_(p)— wherein p is an integer equal to 3 or 4, R_(h)     is R_(hh)—C(O)— or R_(hh)—OC(O)— wherein R_(hh) is one of the groups     —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below     defined, or R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is R_(ii)C(O)— or     R_(ii)OC(O)— wherein R_(ii) is one of the groups —(Y—ONO₂) or     —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below defined; -   Y and Y′ of the groups —(Y—ONO₂) or —(Y′—ONO₂) are each     independently selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   B)

wherein in formula (IB)

-   n⁰ is from 0 to 5 and n¹ is an integer from 1 to 10; -   C)

wherein in formula (IC)

-   n¹ is an integer from 1 to 10, -   n² is 1 and R² is CH₃, X₁ is —C(O)O—; -   D)

wherein in formula (ID):

-   n² is 1 and R² is CH₃, -   Y¹ is —CH═CH(CH₂)_(n) ^(2a)— wherein n^(2a) is 0, -   X₁ is —C(O)O— and n¹ is an integer from 1 to 10; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) and (Y′—ONO₂) are each independently selected     from:

-   more preferably (Y—ONO₂) and (Y′—ONO₂) are equal.     The following are preferred compounds according to the present     invention:

Another embodiment provides compounds of formula (I)

wherein s is 1 and m is 0,

-   s′ and s″ are 0, -   A is a radical of formula (IIa) or (IIl)

wherein R₁ is —C(O)R_(1x) or —C(O)OR_(1x) wherein R_(1x) is the group —(Y—ONO₂) of formula (I) wherein Y is below defined,

-   R₂ in formulas (IIa) and (IIl) is the group R₄

-   R_(a) of formula (IIa) is selected from: -   a) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     benzyl, C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—, 4-imidazolyl-CH₂—; -   b) HS—CH₂—; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is H; -   d) R_(g)C(O)CH₂ or R_(g)C(O)(CH₂)₂—, wherein R_(g) is OH, (CH₃)₃O—     or the group R_(gg)

-   e) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an     integer equal to 3 or 4, R_(h) is H or (CH₃)₃C—OC(O)—, R₁ is H; -   R_(L) of formula (IIl) is H; -   Y of the group —(Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   B)

wherein in formula (IB)

-   n⁰ is from 0 to 5 and n¹ is an integer from 1 to 10; -   C)

wherein in formula (IC)

-   n¹ is an integer from 1 to 10, -   n² is 1 and R² is CH₃, X₁ is —C(O)O—; -   D)

wherein in formula (ID):

-   n² is 1 and R² is CH₃, -   Y¹ is —CH═CH—(CH₂)_(n) ^(2a)— wherein n^(2a) is 0, -   X₁ is —C(O)O— and n¹ is an integer from 1 to 10; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) is selected from:

The following are preferred compounds according to the present invention:

Another embodiment relates to compounds of formula (I)

wherein s and s′ are 1 and m, m′ are 0, s″ is 0,

-   A is a radical of formula (IIa) or (IIl)

wherein

-   R₁ is —C(O)R_(1x), —C(O)OR_(1x) wherein R_(1x) is one of the groups     —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below     defined; -   R₂ is —C(O)OR_(2x), —C(O)NHR_(2x), —C(O)N)CH₃)R_(2xx), wherein     R_(2x) and R_(2xx) are one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of     formula (I) wherein Y and Y′ are below defined, more preferably R₂     is —C(O)OR_(2x) or —C(O)NHR_(2xx); -   R_(a) is selected from: -   a) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     benzyl, C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—, 4-imidazolyl-CH₂—; -   R_(L) in formula (IIl) is H; -   Y and Y′ of the groups (Y—ONO₂) or (Y′—ONO₂) are each independently     selected from -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   B)

wherein in formula (IB)

-   n⁰ is from 0 to 5 and n¹ is an integer from 1 to 10; -   C)

wherein in formula (IC)

-   n¹ is from 1 to 10, -   n² is 1 and R² is CH₃, X₁ is —C(O)O—; -   D)

wherein in formula (ID):

-   n² is 1 and R² is CH₃, -   Y¹ is —CH═CH—(CH₂)_(n) ^(2a)— n^(2a) is 0, -   X₁ is —C(O)O— and n₁ is an integer from 1 to 10; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) and (Y′—ONO₂) are each independently selected     from:

The following are preferred compounds according to the present invention:

Another embodiment relates to compounds of formula (I)

wherein s and s′ are 1, m is 1, m′ is 0, s″ is 0,

-   B at each occurrence is independently selected from:

-   preferably B is

-   more preferably B is:

-   A is a radical of formula

wherein

-   R₁ is —C(O)R_(1x), —C(O)OR_(1x) wherein R_(1x) is —(Y—ONO₂) of     formula (I) wherein Y is below defined; -   R₂ is —C(O)OR_(2x), wherein R_(2x) is the group —[B—(Y′—ONO₂)] of     formula (I) wherein B is as above reported and Y′ is below reported, -   R_(a) is selected from: -   H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—, benzyl,     C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—; NH₂—CO—(CH₂)₂—,     4-imidazolyl-CH₂—; -   R_(L) in formula (IIl) is H, -   Y and Y′ of the groups (Y—ONO₂) and —(Y′—ONO₂) are each     independently selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) and —(Y′—ONO₂) are each independently selected     from:

The following are preferred compounds according to the present invention:

Another embodiment relates to compounds of formula (I)

wherein s and s′ are 1, and s″ are 0, m and m′ are 0,

-   A is a radical of formula

wherein R₁ is —C(O)R_(1x) or —C(O)OR_(1x) wherein R_(1x) is one of the groups —(Y—ONO₂) or (Y′—ONO₂) of formula (I) wherein Y and Y′ are below defined;

-   R₂ is —C(O)OR_(2x), —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx), wherein     R_(2xx) and R_(2x) are one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of     formula (I) wherein Y and Y′ are below defined, more preferably R₂     is —C(O)OR_(2x), —C(O)NHR_(2xx); -   R_(a) is selected from: -   b) HS—CH₂—; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is H, -   d) R_(g)C(O)CH₂— or R_(g)C(O)(CH₂)₂—, wherein R_(g) is OH,     (CH₃)₃CO—, or the group R_(gg)

-   e) R_(h)NH(CH₂)_(p)— or R_(i)NH(═NH)NH—(CH₂)₃—, wherein p is an     integer equal to 3 or 4, R_(h) is H, (CH₃)₃C—OC(O)—, R_(i) is H; -   Y and Y′ of the groups (Y—ONO₂), —(Y′—ONO₂) are each independently     selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) and (Y′—ONO₂) are each independently selected     from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds of formula (I)

wherein s is 1 and m is 0, s′ and s″ are 0,

-   A is a radical of formula

wherein R₁ is H or —C(O)O—C(CH₃)₃,

-   R₂ is —C(O)OH or R₂ is equal to the group R₄

-   R_(a) is selected from: -   b) R_(bx)C(O)—S—CH₂—, R_(bx)OC(O)—S—CH₂—, R_(bx)NH—C(O)S—CH₂—     wherein R_(bx) is the group —(Y—ONO₂) of formula (I) wherein Y is     below defined, -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is R_(xx)C(O)—, R_(xx)OC(O)— or R_(xx)NHC(O)— wherein R_(xx) is the     group —(Y—ONO₂) of formula (I) wherein Y is below defined; -   d) R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂— wherein R_(g) is R_(gx)O—,     R_(gxx)—NH—, or Rg_(xx)—N(CH₃)—, wherein R_(gx) and R_(gxx) are the     group —(Y—ONO₂) of formula (I) wherein Y is below defined, more     preferably R_(g) is R_(gx)O—, R_(gxx)—NH— -   e) R_(h)NH(CH₂)_(p)— wherein p is 3 or 4, and R_(h) is R_(hh)C(O)—     or R_(hh)OC(O)— wherein R_(hh) is the group —(Y—ONO₂) of formula (I)     wherein Y is below defined; -   or R_(i)NH(═NH)NH—(CH₂)₂— wherein R_(i) is R_(ii)C(O)— or     R_(ii)OC(O)— wherein R_(ii) is the group —(Y—ONO₂) of formula (I)     wherein Y is below defined; -   Y of the group (Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) is selected from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds of formula (I)

wherein s and s′ are 1 and m, m′ are 0, s″ is 0,

-   A is a radical of formula

wherein R₁ is H or —C(O)O—C(CH₃)₃—,

-   R₂ is —C(O)OR_(2x), —C(O)NHR_(2xx), —C(O)N(CH₃)R_(2xx) wherein     R_(2x) and R_(2xx) are one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of     formula (I) wherein Y and Y′ are below defined, more preferably R₂     is —C(O)OR_(2x), —C(O)NHR_(2x); -   R_(a) is selected from: -   b) R_(bx)C(O)—S—CH₂—, R_(bx)OC(O)—S—CH₂—, R_(bx)NH—C(O)S—CH₂—     wherein R_(bx) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂) wherein     Y and Y′ are below defined; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is R_(xx)C(O)—, R_(xx)OC(O)— or R_(xx)NHC(O)— wherein R_(xx) is one     the groups —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′     are below reported; -   e) R_(h)NH(CH₂)_(p)— wherein p is 3 or 4, and R_(h) is R_(hh)C(O)—     or R_(hh)OC(O)— wherein R_(hh) is one the groups —(Y—ONO₂) or     —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below reported; -   or R_(a) is R_(i)NH(═NH)NH—(CH₂)₂— wherein R_(i) is R_(ii)C(O)— or     R_(ii)OC(O)— wherein R_(ii) is one the groups —(Y—ONO₂) or     —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below defined; -   Y and Y′ of the groups (Y—ONO₂) or —(Y′—ONO₂) are each independently     selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably —(Y—ONO₂) and —(Y′—ONO₂) are each independently selected     from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds of formula (I)

wherein s and s′ are 1 and m, m′ are 0, s″ is 0,

-   A is a radical of formula

wherein R₁ is H or —C(O)O—C(CH₃)₃,

-   R₂ is —C(O)OR_(2x), —C(O)NHR_(2xx), —C(O)N(CH₃)R_(2xx) wherein     R_(2x) and R_(2xx) are one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of     formula (I) wherein Y and Y′ are below defined, more preferably R₂     is —C(O)OR_(2x), —C(O)NHR_(2xx); -   R_(a) is selected from: -   d) R_(g)C(O)CH₂—, R_(g)C(O)(CH₂)₂—, wherein R_(g) is R_(gx)O—,     R_(gxx)—NH—, R_(gxx)N(CH₃)—, wherein R_(gx) and R_(gxx) are one of     the groups —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′     are below defined, more preferably R_(g) is R_(gx)O— or R_(gxx)—NH—; -   Y and Y′ of the groups (Y—ONO₂) and —(Y′—ONO₂) are each     independently selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) and (Y′—ONO₂) are each independently selected     from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds of formula (I)

wherein s, s′ and s″ are 1, m, m′ and m″ are 0,

-   A is a radical of formula

wherein R₁ is —C(O)R_(1x), —C(O)OR_(1x) wherein R_(1x) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂) or —(Y″—ONO₂) of formula (I) wherein Y, Y′ and Y″ are below defined;

-   R₂ is —C(O)OR_(2x), —C(O)NHR_(2xx), —C(O)N(CH₃)R_(2xx) wherein     R_(2x) and R_(2xx) are one of the groups —(Y—ONO₂) or —(Y′—ONO₂) or     —(Y″—ONO₂) of formula (I) wherein Y, Y′ and Y″ are below reported,     and more preferably R₂ is —C(O)OR_(2x), —C(O)NHR_(2x); -   R_(a) is selected from: -   b) R_(bx)C(O)—CH₂—, R_(bx)OC(O)—S—CH₂—, R_(bx)NH—C(O)S—CH₂— wherein     R_(bx) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂) or —(Y″—ONO₂) of     formula (I) wherein Y, Y′ and Y″ are below reported; -   c) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein R_(x)     is R_(xx)C(O)—, R_(xx)OC(O)— or R_(xx)NHC(O)— wherein R_(xx) is one     of the groups —(Y—ONO₂) or —(Y′—ONO₂) or —(Y″—ONO₂) of formula (I)     wherein Y, Y′ and Y″ are below reported; -   d) R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, wherein R_(g) is R_(gx)O—,     R_(gxx)—NH—, R_(gxx)—N(CH₃)—, wherein R_(gx) and R_(gxx) are one of     the groups —(Y—ONO₂) or —(Y′—ONO₂) or —(Y″—ONO₂) of formula (I)     wherein Y, Y′ and Y″ are below defined, more preferably R_(g) is     R_(gx)O— or R_(gxx)NH—, -   e) R_(h)NH(CH₂)_(p)— wherein p is 3 or 4, and R_(h) is R_(hh)C(O)—     or R_(hh)OC(O)— wherein R_(hh) is one of the groups —(Y—ONO₂) or     —(Y′—ONO₂) or —(Y″—ONO₂) of formula (I) wherein Y, Y′ and Y″ are     below defined, -   or R_(a) is R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is R_(ii)C(O)— or     R_(ii)OC(O)— wherein R_(ii) is one of the groups —(Y—ONO₂) or     —(Y′—ONO₂) or —(Y″—ONO₂) of formula (I) wherein Y, Y′ and Y″ are     below reported; -   Y, Y′ and Y″ of the groups (Y—ONO₂) or —(Y′—ONO₂) or —(Y″—ONO₂) are     each independently selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably —(Y—ONO₂), —(Y′—ONO₂) and —(Y″—ONO₂) are each     independently selected from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds or formula (I)

wherein s and s′ are 1, m and m′ are 0, s″ is 0,

-   A is a radical of formula

wherein R₁ is H or —C(O)—OC(CH₃)₃—;

-   R₃ is —OC(O)R_(3x), OC(O)OR_(3x), —OC(O)—NHR_(3x), wherein R_(3x) is     one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y     and Y′ are below defined; -   R₃ is selected from: -   b″) R_(bx)—C(O)—S—CH₂—, R_(bx)—OC(O)—S—CH₂—, R_(bx)—NH—C(O)S—CH₂—     wherein R_(bx) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of     formula (I) wherein Y and Y′ are below defined; -   c″) R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—, wherein     R_(x) is R_(xx)C(O)—, R_(xx)OC(O)—, R_(xx)NHC(O)— wherein R_(xx) is     one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y     and Y′ are below defined; -   d″) R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, wherein R_(g) is R_(gx)O— or     R_(gxx)NH— wherein R_(gx) and R_(gxx) are one of the groups     —(Y—ONO₂) or —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below     defined; -   e″) R_(h)NH(CH₂)_(p)— wherein p is 3 or 4 and R_(h) is R_(hh)C(O)—     or R_(hh)OC(O)— wherein R_(hh) is one of the groups —(Y—ONO₂) or     —(Y′—ONO₂) of formula (I) wherein Y and Y′ are below defined, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(i) is R_(ii)C(O)— or R_(ii)OC(O)—     wherein R_(ii) is one of the groups —(Y—ONO₂) or —(Y′—ONO₂) of     formula (I) wherein Y and Y′ are below defined; -   Y and Y′ of the groups (Y—ONO₂) or —(Y′—ONO₂) are each independently     selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) and (Y′—ONO₂) are each independently selected     from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds of formula (I)

wherein s is 1, m is 0, s′ and s″ are 0,

-   A is a radical of formula

wherein R₁ is H or —C(O)—OC(CH₃)₃;

-   R₃ is —OC(O)R_(3x), OC(O)OR_(3x), —OC(O)—NHR_(3x), wherein R_(3x) is     the group —(Y—ONO₂) of formula (I) wherein Y is below reported; -   R₃ is selected from: -   a″) H, CH₃, isopropyl, isobutyl, sec-butyl, methylthio-(CH₂)₂—,     benzyl, C₆H₅—CH₂—CH₂—, 3-triptophanyl-CH₂—, NH₂—CO—CH₂—,     NH₂—CO—(CH₂)₂—, 4-imidazolyl-CH₂—; -   Y of the group (Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) is selected from:

The following are preferred compounds according to the present invention:

Another embodiment provides compounds or formula (I)

wherein s is 1 and m is 0, s′ and s″ are 0,

-   A is a radical of formula (IIq)

-   R₁ is H or —C(O)O—C(CH₃)₃—, -   R₂ is —C(O)OR_(2x), —C(O)NHR_(2x) —C(O)N(CH₃) wherein R_(2x) is the     group —(Y—ONO₂) of formula (I) wherein Y is below reported, more     preferably R₂ is —C(O)OR_(2x) or —C(O)NHR_(2x); -   Y of the group (Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂) is selected from:

The following are preferred compounds according to the present invention:

Another embodiment relates to compounds of formula (I)

wherein s is 1 and m is 0, s′ and s″ are 0,

-   A is a radical of formula (IIu)

wherein a is 1 and b is 0;

-   R₁ is H or —C(O)O—C(CH₃)₃, -   R₂ is —C(O)OR_(2x), —C(O)NHR_(2x)—C(O)N(CH₃)R_(2x) wherein R_(2x) is     the group —(Y—ONO₂) of formula (I) wherein Y is below reported, more     preferably R₂ is —C(O)OR_(2x), or —C(O)NHR_(2x), -   R_(x) is H, -   Y of the group (Y—ONO₂) is selected from: -   A)     -   a straight or branched C₂-C₁₀ alkylene     -   a straight or branched C₂-C₁₀ alkylene substituted with a —ONO₂         group; -   E)

wherein in formula (IE)

-   n³ is from 1 to 5, -   n₃ is 0 and n₄ is from 1 to 4, -   n_(3′) is 0 and n_(4′) is from 1 to 4, -   X₂ is —O— or —NH—, -   R² is H, -   preferably (Y—ONO₂), is selected from:

The following are preferred compounds according to the present invention:

The compound's of the present invention show significant advantages over the other known nitric oxide donor compounds, they release nitric oxide (NO) slower, they do not induce hypotension in normotensive subjects and moreover they do not induce increasing of heart rate in hypertensive patients.

The term “C₁-C₂₀ alkylene” as used herein refers to branched or straight chain C₁-C₂₀ hydrocarbon, preferably having from 1 to 10 carbon atoms such as methylene, ethylene, propylene, isopropylene, n-butylene, pentylene, n-hexylene and the like.

The term “C₁-C₁₀ alkyl” as used herein refers to branched or straight chain alkyl groups comprising one to ten carbon atoms, including methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl, octyl and the like.

One term “cycloalkylene” as used herein refers to ring having from 5 to 7 carbon atoms including, but not limited to, cyclopentylene, cyclohexylene optionally substituted with side chains such as straight or branched (C₁-C₁₀)-alkyl, preferably CH₃.

The term “heterocyclic” as used herein refers to saturated, unsaturated or aromatic 5 or 6 members ring, containing one or more heteroatoms selected from nitrogen, oxygen, sulphur, such as for example pyridine, pyrazine, pyrimidine, pyrrolidine, morpholine, imidazole and the like.

As stated above, the invention includes also the pharmaceutically acceptable salts of the compounds of formula (I) and stereoisomers thereof.

Examples of pharmaceutically acceptable salts are either those with inorganic bases, such as sodium, potassium, calcium and aluminium hydroxides, or with organic bases, such as lysine, arginine, triethylamine, dibenzylamine, piperidine and other acceptable organic amines.

The compounds according to the present invention, when they contain in the molecule one salifiable nitrogen atom, can be transformed into the corresponding salts by reaction in an organic solvent such as acetonitrile, tetrahydrofuran with the corresponding organic or inorganic acids.

Examples of organic acids are: oxalic, tartaric, maleic, succinic, citric acids. Examples of inorganic acids are: nitric, hydrochloric, sulphuric, phosphoric acids. Salts with nitric acid are preferred.

The compounds of the invention which have one or more asymmetric carbon atoms can exist as optically pure enantiomers, pure diastereomers, enantiomers mixtures, diastereomers mixtures, enantiomer racemic mixtures, racemates or racemate mixtures. Within the object of the invention are also all the possible isomers, stereoisomers and their mixtures of the compounds of formula (I).

The invention also relates to the use of the compounds of formula (I) or their salts for treating cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases including glaucoma, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolism dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation and vascular diseases.

Another embodiment of the present invention relates to compositions comprising at least a compound of formula (I) or its salt and at least one therapeutic agent selected from anti-inflammatory drugs, drugs used to treat cardiovascular diseases, drugs for treating ocular diseases, drugs for treating respiratory disorders.

Anti-inflammatory drugs include, but are not limited to, non steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs

Drugs used to treat cardiovascular diseases refers to any therapeutic compound, or a pharmaceutically acceptable salt thereof, used to treat any cardiovascular disease. Suitable compounds include, but are not limited to aspirin and derivatives thereof, anti-thrombotic drugs, angiotensin-converting enzyme inhibitors (ACE inhibitors), beta-adrenergic blockers, calcium, channel blockers, angiotensin II receptor antagonists, endothelin antagonists, renin inhibitors, β-adrenergic receptor agonists, cholesterol reducers such as, for example, HMG-CoA reductase inhibitors, including, but not limited to, lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin, atorvastatin. Drugs for treating ocular diseases include, but are not limited to, prostaglandins.

In another object of the invention the two components of the composition above defined are administered simultaneously or sequentially wherein the two components may be administered by the same or different administration pathways.

Another object of the invention provide the use of the composition above reported for the treatment of cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases including glaucoma, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolism dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation and vascular diseases.

Generally the treatment of cardiovascular disease and/or peripheral vascular disorders is a long-term therapy, and it is directed to patients suffering from cardiovascular disease and/or peripheral vascular disorders or inflammatory diseases which suffer from hypertension or diabetes. Long term treatment ranges from about one month to over two years of chronic/maintenance administration.

Another object of the present invention relates to pharmaceutical compositions comprising the composition above reported and non toxic adjuvants and/or carriers usually employed in the pharmaceutical field.

An object of the present invention relates to pharmaceutical compositions comprising at least a compound of formula (I) together with non toxic adjuvants and/or carriers usually employed in the pharmaceutical field.

The invention also relates to the use of the following compounds

-   3-(nitrooxy)propyl 2-(tert-butoxycarbonylamino)-4-phenyl butanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate hydrochloride, -   4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-4-phenylbutanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate hydrochloride, -   (2-(nitrooxy)ethoxy)methyl 2-(tert-butoxycarbonylamino)-4-phenyl     butanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate hydrochloride, -   1-tert-butyl 2-(4-(nitrooxy)butyl)pyrrolidine-1,2-dicarboxylate -   4-(nitrooxy)butyl pyrrolidine-2-carboxylate, -   4-(nitrooxy)butyl pyrrolidine-2-carboxylate hydrochloride, -   1-tert-butyl 2-(3-(nitrooxy)propyl)pyrrolidine-1,2-dicarboxylate, -   3-(nitrooxy)propyl pyrrolidine-2-carboxylate, -   3-(nitrooxy)propyl pyrrolidine-2-carboxylate hydrochloride,     for treating cardiovascular diseases, inflammation, pain, fever,     gastrointestinal disorders, ophthalmic diseases including glaucoma,     hepatic disorders, renal diseases, respiratory disorders,     immunological diseases, bone metabolism dysfunctions, central and     peripheral nervous system diseases, sexual dysfunctions, infectious     diseases, for the inhibition of platelet aggregation and platelet     adhesion, for treating pathological conditions resulting from     abnormal cell proliferation and vascular diseases.

Another object of the present invention relates to compositions comprising at least one of the following compounds:

-   3-(nitrooxy)propyl 2-(tert-butoxycarbonylamino)-4-phenyl butanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate hydrochloride, -   4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-4-phenyl butanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate hydrochloride, -   (2-(nitrooxy)ethoxy)methyl 2-(tert-butoxycarbonylamino)-4-phenyl     butanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate hydrochloride, -   1-tert-butyl 2-(4-(nitrooxy)butyl)pyrrolidine-1,2-dicarboxylate, -   4-(nitrooxy)butylpyrrolidine-2-carboxylate, -   4-(nitrooxy)butylpyrrolidine-2-carboxylate hydrochloride, -   1-tert-butyl 2-(3-(nitrooxy)propyl)pyrrolidine-1,2-dicarboxylate, -   3-(nitrooxy)propylpyrrolidine-2-carboxylate, -   3-(nitrooxy)propylpyrrolidine-2-carboxylate hydrochloride,     and at least one therapeutic agent selected from anti-inflammatory     drugs, drugs used to treat cardiovascular diseases, drugs for     treating ocular diseases, drugs for treating respiratory disorders.     Anti-inflammatory drugs include, but are not limited to, non     steroidal anti-inflammatory drugs and steroidal anti-inflammatory     drugs     Drugs used to treat cardiovascular diseases refers to any     therapeutic compound, or a pharmaceutically acceptable salt thereof,     used to treat any cardiovascular disease. Suitable compounds     include, but are not limited to aspirin and derivatives thereof,     anti-thrombotic drugs, angiotensin-converting enzyme inhibitors (ACE     inhibitors), beta-adrenergic pinchers, calcium channel blockers,     angiotensin II receptor antagonists, endothelin antagonists, renin     inhibitors, β-adrenergic receptor agonists, cholesterol reducers     such as, for example, HMG-CoA reductase inhibitors, including, but     not limited to, lovastatin, simvastatin, pravastatin, fluvastatin,     cerivastatin, atorvastatin.     Drugs for treating ocular diseases include, but are not limited to,     prostaglandins.

In another object of the invention the two components of the composition above defined are administered simultaneously or sequentially wherein the two components may be administered by the same or different administration pathways.

Another object of the invention provides the use of the composition comprising at least one of the following compounds:

-   3-(nitrooxy)propyl 2-(tert-butoxycarbonylamino)-4-phenyl Butanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate, -   3-(nitrooxy)propyl 2-amino-4-phenylbutanoate hydrochloride, -   4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-4-phenyl butanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate, -   4-(nitrooxy)butyl 2-amino-4-phenylbutanoate hydrochloride, -   (2-(nitrooxy)ethoxy)methyl 2-(tert-butoxycarbonylamino)-4-phenyl     butanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate, -   (2-(nitrooxy)ethoxy)methyl 2-amino-4-phenylbutanoate hydrochloride, -   1-tert-butyl 2-(4-(nitrooxy)butyl)pyrrolidine-1,2-dicarboxylate, -   4-(nitrooxy)butyl pyrrolidine-2-carboxylate, -   4-(nitrooxy)butyl pyrrolidine-2-carboxylate hydrochloride, -   1-tert-butyl 2-(3-(nitrooxy)propyl)pyrrolidine-1,2-dicarboxylate, -   3-(nitrooxy)propyl pyrrolidine-2-carboxylate, -   3-(nitrooxy)propyl pyrrolidine-2-carboxylate hydrochloride     and at least one therapeutic agent selected from anti-inflammatory     drugs, drugs used to treat cardiovascular diseases, drugs for     treating ocular diseases, drugs for treating respiratory disorders,     for the treatment of cardiovascular diseases, inflammation, pain,     fever, gastrointestinal disorders, ophthalmic diseases including     glaucoma, hepatic disorders, renal disease, respiratory disorders,     immunological diseases, bone metabolism dysfunctions, central and     peripheral nervous system diseases, sexual dysfunctions, infectious     diseases, for the inhibition of platelet aggregation and platelet     adhesion, for treating pathological conditions resulting from     abnormal cell proliferation and vascular diseases.

An object of the present invention relates to pharmaceutical compositions comprising the composition above reported together with non toxic adjuvants and/or carriers usually employed in the pharmaceutical field.

The daily dose of the active ingredient that should be administered can be a single dose or it can be an effective amount divided into several smaller doses that are to be administered throughout the day. The dosage regimen and administration frequency for treating the mentioned diseases with the compound of the invention and/or with the pharmaceutical compositions of the present invention will be selected in accordance with a variety of factors, including for example age, body weight, sex and medical condition of the patient as well as severity of the disease, route of administration, pharmacological considerations and eventual concomitant therapy with other drugs. In some instances, dosage levels below or above the aforesaid range and/or more frequent may be adequate, and this logically will be within the judgment of the physician and will depend on the disease state.

The compounds of the invention may be administered orally, parenterally, rectally or topically, by inhalation or aerosol, in formulations eventually containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles as desired. Topical administration may also involve the use of transdermal administration such as transdermal patches or iontophoresis devices. The term “parenteral” as used herein, includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques.

Injectable preparations, for example sterile injectable aqueous or oleaginous suspensions may be formulated according to known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent. Among the acceptable vehicles and solvents are water, Ringer's solution and isotonic sodium chloride. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono or diglycerides, in addition fatty acids such as oleic acid find use in the preparation of injectables.

Suppositories for rectal administration of the drug can be prepared by mixing the active ingredient with a suitable non-irritating excipient, such as cocoa butter and polyethylene glycols.

Solid dosage forms for oral administration may include capsules, tablets, pills, powders, granules and gels. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, e.g. lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavouring and the like.

Synthesis Procedure

1. The Compounds of General Formula (I)

wherein:

-   s is equal to 1; -   m, m′, m″, s′ and s″ are 0 -   Y is as above defined, -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x) and it binds the group —Y—ONO₂, R₂     is —COOH; -   in formula (IIn) R_(n) is —C(O)—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)R_(hh) and it binds the group —Y—ONO₂ -   R_(a) of formula (IIa) is selected in group a) -   R_(c) of formula (IIc) is selected in group a′) -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows -   1a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 1., A is a radical of formula     (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₂ is     —C(O)OC(CH₃)₃; R₁, R_(a), R_(c), R_(h), R_(n), d, and d′ are as     defined in 1., with anhydrous or aqueous organic or inorganic acid     to hydrolyze the t-butyl ester following procedure well known in the     literature. -   1b) by reacting a compound of formula A with a compound of formula     (IIIa)     A+HOOC—Y—ONO₂  (IIIa)     wherein Y is as above defined and A is selected from (IIa)-(IIm),     (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₁, is —H and R₂ is     —C(O)O(CH₃)₃; -   in formula (IIn) R_(n) is H, or is —(CH₂)₂—NH—R_(h) wherein R_(h) is     H; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula, (IIt) d and d′ are as above defined;     in the presence of a condensing agent such as     dicyclohexylcarbodiimide (DCC) or N,N′-carbonyldiimidazol (CDI) or     other known condensing reagents such as     O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium     hexafluorophosphate (HATU), in the presence or not of     1-Hydroxybenzotriazole (HOBT) in solvent such as DMF, THF,     chloroform at a temperature in the range from −5° C. to 80° C. in     the presence or not of a base as for example DMAP.     The nitric acid ester compounds of formula (IIIa) can be obtained     from the corresponding alcohols of formula HOOC—Y—OH (IIIb), that     are commercially available, by reaction with nitric acid and acetic     anhydride in a temperature range from −51° C. to 0° C. or reacting     the corresponding halogen derivatives of formula HOOC—Y-Hal (IIIc)     wherein Hal is an halogen atom preferably Cl, Br, I, that are     commercially available, with AgNO₃ as known in the literature.     Alternatively the reaction with AgNO₃ can be performed under     microwave irradiation in solvents such acetonitrile or THF at     temperatures in the range between about 100-180° C. for time range     about 1-60 min.     Dinitrated compounds of formula (IIIa) can be also directly prepared     with I₂ and AgNO₃ starting from carboxylic acids with a double bond     in the chain as described in WO 2005/070868.     Compounds (IIIa) can be also prepared from the corresponding Tosyl     derivative (IIId) HOOC—Y—OTs by reacting with AgNO₃ or MetalNO₃     wherein Metal is Li⁺, Na⁺, K⁺, in solvents such acetonitrile or DMF     at refluxing temperature or under microwave irradiation at     temperatures in the range between about 100-180° C. for time range     about 1-120 min. -   1b′) alternatively compound A reported in 1b) can be reacted with a     compound of formula (IIIe):     A+Act-CO—Y—ONO₂  (IIIe)     wherein Y is as above defined; Act is an Halogen atom or a     carboxylic acid activating group used in peptide chemistry such as:

the reaction is generally carried out in presence of a inorganic or organic base in an aprotic polar/non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures range between 0°-80° C. or in a double phase system H₂O/Et₂O at temperatures range between 20°-40° C.; or in the presence of DMAP and a Lewis acid such as Sc(OTf)₃ or Bi(OTf)₃ in solvents such as DMF, CH₂Cl₂. The compounds of formula (IIIe) can be obtained as described in WO 2006/008196.

-   1c) compounds A reported in 1b) are commercially available or can be     prepared by reacting a compound of formula A₁ wherein A₁ is a     radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein R₂ is —COOH, R₁ and R₆ are substituted by the Fmoc     protective group and R_(a), R_(c), d and d′ are as defined in 1.,     with tert-butyl alcohol and sulphuric acid or other methods to     obtain a tert-butyl ester well known in the literature. Eventually     removing the Fmoc protective group using methods known in the     literature.     Compounds A₁ are commercially available or can be prepared by the     correspondent compounds A₂:     A₂→A₁     wherein A₂ is a radical of formula (IIa)-(IIm), (IIo)-(IIr),     (IIt)-(IIu) and (IIn) wherein R₂ is —COOH, and R₁ is —C(O)OC(CH₃)₃,     R_(n) is —C(O)OC(CH₃)₃ or is —(CH₂)₂—NH—C(O)OC(CH₃)₃, R_(a), R_(c) d     and d′ are as defined in 1., by converting the —BOC protective group     into the Fmoc protective group as described in the literature. -   Compounds A₂ are commercially available. -   2. Alternatively compounds of formula (I) described in 1. can be     obtained: -   2a) by reacting a compound of formula (IVa)     A-(Y—X)  (IVa)     wherein X is an halogen atom or tosyl group, Y is as above defined     and A is as above defined in 1b), with AgNO₃ or MetalNO₃ as above     described in 1b).     Compounds (IVa) can be obtained by reacting compound A as above     defined in 1b), with compounds (IIIc) as above described in 1b),     with a condensing reagent such as DCC or CDI as above described in     1b); -   or -   2a′) alternatively compounds of formula (I) described in 1a) can be     obtained by reacting a compound of formula (Va):     A-(Y—OH)  (Va)     wherein A and Y are as above defined in 1a), with triflic     anhydride/tetraalkylammonium nitrate salt in an aprotic     polar/non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures     range between −78° to 80° C.     Compounds (Va) can be obtained by reacting compound A as defined in     1b), with compounds (IIIb) with a condensing reagent as above     described for (IIIa) in 1b). -   3. The compounds of general formula (I) wherein: -   s is equal to 1; -   m, m′, m″, s′ and s″ are 0 -   Y is as above defined, -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and it binds the group —Y—ONO₂, -   R₂ is —COOH; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), and it binds the group —Y—ONO₂ -   R_(a) of formula (IIa) is selected in group a) -   R_(c) of formula (IIc) is selected in group a′) -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows -   3a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 3., A is a radical of formula     (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₂ is     —C(O)OC(CH₃)₃; R₁, R_(a), R_(c), R_(n), R_(h), d and d′ are as     defined in 3. with anhydrous or aqueous organic or inorganic acid to     hydrolyze the t-butyl ester following procedure well known in the     literature. -   3b) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act-(O)C—O—Y—ONO₂  (IIIf)     wherein A is as above reported in 1b), Y is as above reported and     Act is as above defined in 1b′).

The reaction is generally carried out in presence of a inorganic or organic base in an aprotic polar/non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures range between 0°-80° C. or in a double phase system H₂O/Et₂O at temperatures range between 20°-40° C.; or in the presence of DMAP and a Lewis acid such as Sc(OTf)₃ or Bi(OTf)₃ in solvents such as DMF, CH₂Cl₂. Compounds (IIIf) are obtained as described in WO 2006/008196.

-   4. The compounds of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″ are equal to 0; -   Y is as above defined; -   B is:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —H and R₂ is —C(O)OR_(2x) and binds the group     —B—Y—ONO₂ -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be obtained as follows: -   4a) reacting a compound of formula (I) wherein B, s, s′, s″, m, m′,     m″, Y, Y′ and Y″ are as above defined in 4., A is a radical of     formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₂,     R_(a), R_(c), d and d′ and of are as defined in 4., R₁ is     —C(O)OC(CH₃)₃; R_(n) or is —C(O)OC(CH₃)₃ or is     —(CH₂)₂—NH—C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid as well known in     the literature to remove all the —BOC protective groups. -   4b) by reacting a compound of formula A with compounds of formula     (IIIg)     A+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     wherein Y is as above described, Hal is an halogen atom and W₁ is     —CH₂— or —CH(CH₃)—, and A is a compound of formula (IIa)-(IIm),     (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₁ is —C(O)OC(CH₃)₃ and     R₂ is —COOH; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d and d′ are as above defined; -   in formula (IIn) R_(n) is —C(O)OC(CH₃)₃ or is     —(CH₂)₂—NH—C(O)OC(CH₃)₃; -   in the presence of a inorganic or organic base in an aprotic     polar/non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures     range between 0° to 100° C. or in a double phase system H₂O/Et₂O at     temperatures range between 20°-40° C. Compounds A as above defined     are commercially available.

The compounds of formula (IIIg) are obtained by reacting the commercially available haloalkylhalocarbonate of formula (IIIh) Hal-W₁—OC(O)Hal  (IIIh) wherein Hal and W₁ are as above defined, with a compound of formula (IIIi) HO—Y—ONO₂  (IIIi) wherein Y is as above defined, in the presence of a inorganic or organic base in an aprotic polar or in an aprotic non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures range between 0° to 80° C.

Dinitrated compounds of formula (IIIi) can be also prepared with I₂ and AgNO₃ or by Sharpless oxidation and then Nitration with Acetic anhydride and nitric acid starting from a double bond in the chain as described in WO 2005/070868.

The compounds of formula (IIIi) are obtained by reacting compounds of formula HO—Y-Hal (IIIj) wherein Y and Hal are as above defined or compounds of formula HO—Y—OTs (IIIk) wherein Ts is the tosyl group, with AgNO₃ on MetalNO₃ in a suitable organic solvent such as acetonitrile or tetrahydrofuran (THF) under nitrogen in the dark at temperatures range between 20°-80° C.; alternatively the reaction with AgNO₃ or MetalNO₃ can be performed under microwave irradiation in solvents such acetonitrile or THF at temperatures in the range between about 100°-180° C. for time range about 1-120 min as already described in 1b)

The compounds of formula (IIIj) and (IIIk) are commercially available or can be obtained from commercially available compounds HO—Y—OH (IIIl) with methods well known in the literature.

-   5. Alternatively compounds (I) described in 4a) can be obtained -   5a) by reacting compounds of formula (VIa) wherein A, B and Y have     been already defined in 4. with tetraalkylammonium nitrate and     triflic anhydride as previously described     A-(B)—(Y—OH)  (VIa) -   Compounds (VIa) can be obtained by reacting compounds A as defined     in 4b) with compounds (IIIm):     Hal-W₁—OC(O)O—Y—OH  (IIIm) -   Using the same procedure described in 4b). Compounds (IIIm) are     prepared from commercially available compounds Hal-W₁—OC(O)Hal     (IIIh) by reacting with compounds HO—Y—OH (IIIl) in the presence of     a inorganic or organic base in an aprotic polar or in an aprotic     non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures range     between 0°-80° C., using a ratio (IIIh)/(IIIl) 1:1. -   6. The compounds of general formula (I) wherein: -   s and m are equal to 1 -   s′, s″, m′, m″ are equal to 0; -   Y is as above defined; -   B is:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —H and R₂ is —C(O)OR_(2x) and binds the group     —B—Y—ONO₂ -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a) -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be obtained as follows: -   6a) reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′ and Y″ are as above defined in 6., A is a radical of formula     (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₂, R_(a),     and R_(c), d and d′ as defined in 6., R₁ or R_(n) is —C(O)OC(CH₃)₃     or —(CH₂)₂—NH—C(O)OC(CH₃)₃; with anhydrous or aqueous organic or     inorganic acid as well known in the literature to remove all the     —BOC protective groups. -   6b) by reacting a compound of formula A with compounds of formula     (IIIn)     A+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     wherein Y is as above described, Hal is an halogen atom and W₁ is     —CH₂— or —CH(CH₃)—, and A is a compound of formula (IIa)-(IIm),     (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₁ is —C(O)OC(CH₃)₃ and     R₂ is —COOH; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIn) R_(n) is —C(O)OC(CH₃)₃ or is —(CH₂)₂—NHR_(h)     wherein R_(h) is —C(O)OC(CH₃)₃; -   in formula (IIt) d is an integer from 3 to 5, d′ is 0; -   in the presence of a inorganic or organic base in an aprotic     polar/non-polar solvent such as DMF, THF or CH₂Cl₂ at temperatures     range between 0°-100° C. or in a double phase system H₂O/Et₂O at     temperatures range between 20°-40° C.     The compounds of formula (IIIn) are obtained by reacting a compound     W₂—CHO, wherein W₂ is H—, CH₃— with compounds of formula (IIIe),     wherein Y and Act are as above defined, and ZnCl₂ as described in     the literature (Steven K. Davidsen and al., J. Med Chem., 37(26),     4423, 1994).     W₂—CHO+ZnCl₂+Act-(O)C—Y—ONO₂  (IIIe) -   7. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″ are equal to 0; -   Y is as above defined; -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —H and R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₂)R_(2xx) and R₂ binds the group —Y—ONO₂ -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be obtained as follows: -   7a) reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′ and Y″ are as above defined in 7., A is a radical of formula     (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₂, R_(a)     R_(c), d and d′ are as defined in 7., R₁ is —C(O)OC(CH₃)₃; R_(n) is     —C(O)OC(CH₃)₃ or is —(CH₂)₂—NHR_(h) wherein R_(h) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid as well known in     the literature to remove all the —BOC protective groups. -   7b) by reacting a compound of formula A with compounds of formula     (IIIo)     W₃NH—Y—ONO₂  (IIIo)     wherein Y is as above described, W₃ is H or —CH₃, A has been already     defined in 4b), in the presence of a condensing agent like     dicyclohexylcarbodiimide (DCC) or N,N′-carbonyldiimidazol (CDI) or     other known condensing reagents such as     O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium     hexafluorophosphate (HATU) in the presence or not of     1-Hydroxybenzotriazole (HOBT) in solvent such as DMF, THF,     chloroform at a temperature in the range from −5° C. to 60° C. in     the presence or not of a base as for example DMAP. Compounds (IIIo)     can be prepared from compounds (IIIp), wherein Y and W₃ are as above     defined by hydrolysing the BOC protecting group as known in the     literature:     (CH₃)₃CO(O)C—NW₃—Y—ONO₂  (IIIp) -   Compounds (IIIp) can be prepared from compounds (IIIq) or (IIIr)     wherein W₃, Y, Hal and Ts are as above described, by reacting with     AgNO₃ as already described for analogous compounds:     (CH₃)₃CO(O)C—NW₃—Y-Hal  (IIIq)     (CH₃)₃CO(O)C—NW₃—Y—OTs  (IIIr)     Alternatively compounds (IIIp) can be prepared from compounds (IIIs)     by reacting with tetraalkylammonium nitrate as already described for     analogous compounds.     (CH₃)₃CO(O)C—NW₃—Y—OH  (IIIs)     Compounds (IIIq) and (IIIr) can be prepared from compounds (IIIs) by     halogenation or tosylation as known an the literature. Compounds     (IIIs) are obtained by known methods from compounds (IIIt) that are     commercially available.     W₃NH—Y—OH  (IIIt) -   8. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″ are equal to 0; -   Y is as above defined; -   A is a radical of formula ((IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —H and R₂ is —C(O)OR_(2x) and binds the group     —Y—ONO₂ -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be obtained as follows: -   8a) reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′ and Y″ are as above defined in 8., A is a radical of formula     (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₂, R_(a),     R_(c) d and d′ are as defined in 8., R₁ is —C(O)OC(CH₃)₃; R_(n) is     —C(O)OC(CH₃)₃ or is —(CH₂)₂—NHR—C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid as well known in     the literature to remove all the —BOC protective groups. -   8b) by reacting a compound of formula A with compounds of formula     (IIIi)     HO—Y—ONO₂  (IIIi)     wherein Y is as above described, A is a radical of formula     (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₁ is     —C(O)OC(CH₃)₃; R₂ is —COOH or is equal to R_(2a) wherein R_(2a) is     the group —COAct wherein Act is as above described in 1b′) and is a     carboxylic acid activating group, R_(a), R_(c) d and d′ are as     defined in 8., R_(n) is —C(O)OC(CH₃)₃ or is     —(CH₂)₂—NHR—C(O)OC(CH₃)₃; -   in the presence of a condensing agent such as     dicyclohexylcarbodiimide (DCC) or N,N′-carbonyldiimidazol (CDI) or     other known condensing reagents such as     O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium     hexafluorophosphate (HATU), in the presence or not or     1-Hydroxybenzotriazole (HOBT) in solvent such as DMF, THF or     chloroform at a temperature in the range from −5° C. to 60° C. in     the presence or not of a base as for example DMAP when R₂ is —COOH;     or in the presence of equimolar amount of DMAP -   in solvent such as DMF, THF, chloroform at a temperature in the     range from −5° C. to 60° C. when R₂ is equal to R_(2a). -   9. Alternatively the compounds of formula (I) as defined in 8a) can     be obtained as follow: -   9a) reacting a compound of formula (IVb)     A-Y—X  (IVb)     wherein Y is as above defined and A is as above defined in 8a) and X     is an halogen atom or a tosyl group, by reacting with AgNO₃ or     MetalNO₃ as above described. Compounds (IVb) can be obtained by     reacting compound A defined as above in 6b), with compounds (IIIj)     or (IIIk)     HO—Y-Hal  (IIIj)     HO—Y—OTs  (IIIk) -   with a condensing reagent such as DCC or CDI or HATU as shove     defined in 6b). -   10. Alternatively the compounds of formula (I) as defined in 8a) can     be obtained -   10a) by reacting a compound of formula (Vb)     A-Y—OH  (Vb)     wherein Y is as above defined, and A is as already defined in 8)     with triflic anhydride/tetraalkylammonium nitrate as already     described. Compounds (Vb) can be obtained by reacting components A     as above described in 8b) with a compound of formula HO—Y—OH (IIIl)     with a condensing reagent such as DCC or CDI or HATU as above     defined in 8b) using a ratio A/(IIIl) 1:1. -   11. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined, -   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)R_(1x) and binds the group —Y—ONO₂, R₂ is —C(O)OR_(2x)     and binds the group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   11a) by reacting compounds of formula (I) as defined in 1., obtained     with the procedure described in 1. with compounds (IIIi)

Wherein Y and Y′ are equal or different and are as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x) and binds the group —Y—ONO₂, R₂ is     —COOH; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 8b). -   12. The compounds of general formula (I) wherein: -   s and a′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined, -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and binds the group —Y—ONO₂; R₂ is     —C(O)OR_(2x) and R₂ binds the group —Y—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   12a) by reacting compounds of formula (I) obtained with the     procedure described in 3. with compounds (IIIi)

Wherein Y and Y′ are equal or different and are as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and binds the group —Y—ONO₂, R₂ is     —COOH; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 8b). -   13. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined, -   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)—R_(1x) and binds the group —Y—ONO₂, R₂ is —C(O)NHR_(2xx)     or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   13a) by reacting compounds of formula (I) obtained with the     procedure described in 1. with compounds (IIIo)

Wherein Y and Y′ are equal or different and are as above defined, W₃ is as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x) and binds the group —Y—ONO₂, R₂ is     —COOH; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 7b). -   14. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined, -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and R₁ binds the group —Y—ONO₂, R₂     is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and R₂ binds the group     —Y—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(n)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   14a) by reacting compounds of formula (I) obtained with the     procedure described in 3. with compounds (IIIo)

Wherein Y and Y′ are equal or different and are as above defined, W₃ is as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and binds the group —Y—ONO₂, R₂ is     —COOH; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 7b). -   15. The compounds of general formula (I) wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   B is:

-   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)—R_(1x) and binds the group —Y—ONO₂, R₂ is —C(O)OR_(2x)     and R₂ binds the group —B—Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   15a) By reacting compounds of formula (I) obtained with the     procedure described in 1. with compounds (IIIg)     A-Y—ONO₂+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     wherein Y is as above described, Hal is an halogen atom and W₁ is     —CH₂— or —CH(CH₃)—, and A has the following meanings: -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x)— and binds the group —Y—ONO₂, R₂ is     —COOH; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 4b). -   16. The compounds of general formula (I) wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   B is:

-   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)—R_(1x) and binds the group —Y—ONO₂, is R₂ is     —C(O)OR_(2x) and binds the group —B—Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂, -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows -   16a) by reacting compounds of formula (I) obtained with the     procedure described in 1, with compounds (IIIn)

wherein 1 is as above described, Hal is an halogen atom and W₁ is —CH₂— or —CH(CH₃)—, and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x)— and binds the group —Y—ONO₂, -   R₂ is —COOH; -   in formula (IIn) R_(n) is —C(O)—R_(nx)— or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂, -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 6b). -   17. The compounds of general formula wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   B is:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and R₂ is —C(O)OR_(2x) and R₁     binds the group —Y—ONO₂ and R₂ binds the group —B—Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂, -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   17a) by reacting compounds of formula (I) obtained with the     procedure described in 3. with compounds (IIIg)

wherein Y is as above described, Hal is an halogen atom and W₁ is —CH₂— or —CH(CH₃)—, and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x)— binds the group —Y—ONO₂, R₂ is     —COOH; -   in formula (IIn) R_(n) is —C(O)O—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 4b). -   18. The compounds of general formula (I) wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   B is:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and R₂ is —C(O)OR_(2x) and R₁     binds the group —Y—ONO₂ and R₂ binds the group —B—Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   18a) By reacting compounds of formula I obtained with the procedure     described in 3. with compounds (IIIn)

wherein Y is as above described, Hal is an halogen atom and W₁ is —CH₂— or —CH(CH₃)—, and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x)— and binds the group —Y—ONO₂, R₂     is —COOH; -   in formula (IIn) R_(n) is —C(O)O—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 6b). -   19. Alternatively the compounds of general formula (I) described in     procedure 11. wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined, -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x) and R₂ is —C(O)OR_(2x) and R₂ binds     the group —Y—ONO₂ and R₂ binds the group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y′—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   19a) By reacting compounds of formula (I) obtained with the     procedure described in 8. with compounds (IIIa) or (IIIe)

Wherein Y and Y′ are equal or different and are as above defined, Act is as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂, R₁ is     —H; -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 1b) or 1b′). -   20. Alternatively the compounds of general formula (I) described in     procedure 12., wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)O—R_(1x) and R₂ is —C(O)OR_(2x) and R₂ binds the group     —Y—ONO₂ and R₁ binds the group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y′—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   20a) By reacting compounds of formula (I) obtained with the     procedure described in 8. with compounds (IIIf)

-   Wherein Y and Y′ are equal or different and are as above defined and     A has the following meanings: -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂, R₁ is     —H; -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 3b). -   21. Alternatively the compounds of general formula (I) described in     procedure 13. wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined, -   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)—R_(1x) and R₂ is —C(O)NHR_(2xx) or —C(O)NCH₃—R_(2xx) and     R₂ binds the group —Y—ONO₂ and R₁ binds the group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y′—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   21a) By reacting compounds of formula (I) obtained with the     procedure described in 7. with compounds (IIIa) or (IIIe)

wherein Y and Y′ are equal or different and are as above defined, Act is as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds     the group —Y—ONO₂, R₁ is —H; -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 1b) or 1b′). -   22. Alternatively the compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0, Y, Y′ can be equal or different and are as     above defined; -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds the group —Y—ONO₂ and R₁ binds the     group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y′—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   22a) By reacting compounds of formula (I) obtained with the     procedure described in 7. with compounds (IIIf)

wherein Y and Y′ are equal or different and are as above defined and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds     the group —Y—ONO₂, R₁ is —H; -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 3b). -   23. Alternatively the compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   B is:

-   A is selected from (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and (IIn)     wherein: -   R₁ is —C(O)—R_(1x) and R₂ is —C(O)OR_(2x) and R₂ binds the group     —B—Y—ONO₂ and R₁ binds the group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)—R_(hh), R_(n) or R_(h) binds the group     —Y′—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   23a) By reacting compounds of formula (I) obtained with the     procedure described in 4. or 6. with compounds (IIIa) or (IIIe)

wherein Y, and Y′ are equal or different and are as above defined, Act and B are as above described and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds the group     —B—Y—ONO₂ -   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 1b) or 1b′). -   24. Alternatively the compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   B is:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and R₂ is —C(O)OR_(2x) and R₂     binds the group —B—Y—ONO₂ and R₁ binds the group —Y′—ONO₂; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), R_(n) or R_(h) binds the group     —Y′—ONO₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows: -   24a) by reacting compounds of formula (I) obtained with the     procedure described in 4. or 6. depending on the meanings of B with     compounds (IIIf)

wherein Y, and Y′ are equal or different and are as above defined, Act is as above described and A has the following meanings:

-   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds the group     —B—Y—ONO₂ -   B is:

-   in formula (IIn) R_(n) is —H or is —(CH₂)₂—NH₂; -   R_(a) of formula (IIa) is selected in group a), -   R_(c) of formula (IIc) is selected in group a′), -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     using the same procedure described in 3b). -   25. The compounds of general formula (I) wherein: -   s, is equal to 1; -   s′ s″, m, m′, m″, are 0 -   Y is as above defined; -   A is a radical of formula (IIs) wherein R₁ is —C(O)—R_(1x) and it     binds the group —Y—ONO₂, R₃ is —OH and R_(s) is selected in group     a″), can be prepared as follows -   25a) by reacting compounds of formula A with a compound of formula     (IIIa) or (IIIe):     HOOC—Y—ONO₂  (IIIa)     ActOC—Y—ONO₂  (IIIe)     wherein Y is as above defined, Act is as above described and A is a     compound of formula (IIs) wherein R₁ is —H, R₃ is —OH and R_(s) is     selected in group a″), using the same procedure described in 1b) or     1b′) using a ratio A/(IIIa) or A/(IIIe) 1:1.     Compounds A are commercially available. -   26. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is a radical of formula (IIs) wherein R₁ is —C(O)O—R_(1x) and it     binds the group —Y—ONO₂, R₃ is —OH and R_(s) is selected in group     a″), can be prepared as follows: -   26a) by reacting compounds of formula A with a compound of formula     (IIIf):     Act-(O)C—O—Y—ONO₂  (IIIf)     wherein Y is as above defined, Act is as above described and A is a     compound of formula (IIs) described, in 25a) wherein R₁ is —H, R₃ is     —OH and R_(s) is selected in group a″), using the same procedure     described, in 3b) using a ratio A/(IIIf) 1:1. -   27. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)—R_(3x) and it     binds the group —Y—ONO₂; R₁ is —H and R_(s) is selected in group     a″), can be prepared as follows: -   27a) by reacting compounds of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 27., A is a radical of formula     (IIs) R₁ is —C(O)OC(CH₃)₃; R₃ and R_(s) are as defined in 27.; with     anhydrous or aqueous organic or inorganic acid to hydrolyze the —BOC     protective groups following procedure well known in the literature. -   27b) by reacting a compound of formula A with a compound of formula     (IIIe)     Act-(O)C—Y—ONO₂  (IIIe)     wherein Y and Act are as above defined; A is a compound of formula     (IIs) wherein R₁ is —C(O)OC(CH₃)₃, R₃ is —OH and R_(s) is selected     in group a″), using the same procedure described in 1b′). Compounds     A are commercially available. -   28. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)O—R_(3x) and it     binds the group —Y—ONO₂; R₁ is —H and R_(s) is selected in group     a″), can be prepared as follows: -   28a) by reacting compounds of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 28., A is a radical of formula     (IIs) R₁ is —C(O)OC(CH₃)₃; R₃ and R_(s) are as defined in 28. with     anhydrous or aqueous organic or inorganic acid to hydrolyze the —BOC     protective groups following procedure well known in the literature. -   28b) By reacting a compound of formula A with a compound of formula     (IIf)     Act-(O)C—O—Y—ONO₂  (IIIf)     wherein Y and Act are as above defined; A is a compound of formula     (IIs) described in 27a) wherein R₁ is —C(O)OC(CH₃)₃, R₃ is —OH and     R_(s) is selected in group a″), using the same procedure described     in 3b) -   29. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)—NH—R_(3x)— and     it binds the group —Y—ONO₂; R₁ is —H and R_(s) is selected in group     a″), can be prepared as follows: -   29a) by reacting compounds of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 29., A is a radical of formula     (IIs) R₁ is —C(O)OC(CH₃)₃; R₃ and R_(s) are as defined in 29. with     anhydrous or aqueous organic or inorganic acid to hydrolyze the —BOC     protective groups following procedure well known in the literature. -   29b) by reacting a compound of formula A with a compound of formula     (IIIu)     Act-(O)C—NH—Y—ONO₂  (IIIu)     wherein Y and Act are as above defined; A is a compound of formula     (IIs) described in 27b) wherein R₁ is —C(O)OC(CH₃)₃, R₃ is —OH and     R_(s) is selected in group a″), in the presence of a inorganic or     organic base in an aprotic polar/non-polar solvent such as DMF, THF,     or CH₂Cl₂ at temperatures range between 0°-100° C. for time range of     1-60 hrs, or under microwave irradiation in the presence of DMAP and     a Lewis acid such as Sc(OTf)₃ or Bi(OTf)₃ in solvents such as DMF,     CH₂Cl₂ at temperatures range between 60°-120° C. for time range of     1-120 min;     Compounds (IIIu) can be prepared from compounds Act-(O)C—NH—Y—OH     (IIIv) by nitrating reactions with tetraalkylammonium nitrate as     already described. Compounds (IIIv) can be prepared from     commercially available Act-CO-Hal (IIIw) and compounds W₃NH—Y—OH     (IIIt) with the proviso that in (IIIt) W₃ has only the meaning of     —H. -   30. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y, Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)—R_(3x) and it     binds the group —Y—ONO₂ or the group —Y—ONO₂; R₁ is —C(O)—R_(1x) and     it binds the group —Y—ONO₂ or the group —Y′—ONO₂; -   R_(s) is selected in group a″), can be prepared as follows: -   30a) Y and Y′ are equal     by reacting compounds of formula A described in 25a) with a compound     of formula (IIIe)     Act-(O)C—Y—ONO₂  (IIIe)     wherein Y and Act are as above defined; A is a compound of formula     (IIs) wherein R₁ is —H, R₃ is —OH and R_(s) is selected in group     a″), using a ratio A/(IIIe) 1:2 and applying the same procedure     described in 1b′). -   30a′) Y and Y′ are equal or different     by reacting compounds of formula (I) prepared in 25. with a compound     of formula (IIIe)     A-Y—ONO₂+Act-(O)C—Y′—ONO₂  (IIIe)     wherein Y, Y′ and Act are as above defined; A is a compound of     formula (IIs) wherein R₁ is —C(O)—R_(1x) and binds the group     —Y—ONO₂, R₃ is —OH and R_(s) is selected in group a″), applying the     same procedure described in 1b′). -   30a″) Y and Y′ are equal or different     by reacting compounds of formula (I) prepared in 27. with a compound     of formula (IIIe)     A-Y—ONO₂+Act-(O)C—Y′—ONO₂  (IIIe)     wherein Y, Y′ and Act are as above defined; A is selected from (IIs)     wherein R₁ is —H, R₃ is —OC(O)—R_(3x) and R_(s) is selected in group     a″), applying the same procedure described in 1b′). -   31. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)O—R_(3x)— and it     binds the group —Y—ONO₂ or the group —Y′—ONO₂; R₁ is —C(O)—R_(1x)     and it binds the group —Y—ONO₂ or the group —Y′—ONO₂, R_(s) is     selected in group a″), can be prepared as follows: -   31a) by reacting compounds of formula (I) obtained in procedure 25.     with a compound of formula (IIIf)     A-Y—ONO₂+Act-(O)C—O—Y′—ONO₂  (IIIf)     wherein Y, Y′ and Act are as above defined; A is a radical of     formula (IIs) wherein R₁ is —C(O)—R_(1x) and it binds the group     —Y—ONO₂, R₃ is —OH and R_(s) is selected in group a″), applying the     same procedure described in 28b). -   31a′) alternatively by reacting compounds of formula (I) prepared as     described in 28. with a compound of formula (IIIe)     A-Y—ONO₂+Act-(O)C—Y′—ONO₂  (IIIe)     wherein Y, Y′ and Act are as above defined; A is the radical of     formula (IIs) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and R₃ binds     the group —Y—ONO₂, R_(s) is selected in group a″), applying the same     procedure described in 25a). -   32. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)—NH—R_(3x) and     it binds the group —Y—ONO₂; R₁ is —C(O)—R_(1x) and it binds the     group —Y′—ONO₂, R_(s) is selected in group a″), can be prepared as     follows: -   32a) by reacting compounds of formula (I) obtained in procedure 29.     with a compound of formula (IIIe)

wherein Y, Y′ and Act are as above defined; A is a radical of formula (IIs) wherein R₁ is —H, R₃ is —OC(O)—NH—R_(3x) it binds the group —Y—ONO₂, R_(s) is selected in group a″), applying the same procedure described in 25a).

-   33. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)—R_(3x) and it     binds the group —Y′—ONO₂; R₁ is —C(O)O—R_(1x) and it binds the group     —Y—ONO₂, R_(s) is selected in group a″), can be prepared as follows: -   33a) by reacting compounds of formula (I) obtained in procedure 26.     with a compound of formula (IIIe)

wherein Y, Y′ and Act are as above defined; A is a radical of formula (IIs) wherein R₁ is —C(O)O—R_(1x) and it binds the group —Y—ONO₂, R₃ is —OH and R_(s) is selected in group a″), applying the same procedure described in 27b).

-   34. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)O—R_(3x) and it     binds the group —Y—ONO₂ or the group —Y′—ONO₂, R₁ is —C(O)O—R_(1x)     and it binds the group —Y—ONO₂ or the group —Y′—ONO₂, R_(s) is     selected in group a″), can be prepared as follows: -   34a) Y and Y′ are equal;     by reacting compounds of formula A described in 25a) with a compound     of formula (IIIf)     A+Act-(O)C—O—Y′—ONO₂  (IIIf)     wherein Y, Y′ and Act are as above defined; A is a compound of     formula (IIs) wherein R₁ is —H, R₃ is —OH and R_(s) is selected in     group a″), using a ratio A/(IIIf) 1:2 and applying the same     procedure described in 3b). -   34a′) Y and Y′ are equal or different     by reacting compounds of formula (I) prepared in 26. with a compound     of formula (IIIf)

wherein Y, Y′ and Act are as above defined; A is a radical of formula (IIs) wherein R₁ is —C(O)O—R_(1x) and it binds the group —Y—ONO₂ and R₃ is —OH, R₃ is selected in group a″); applying the same procedure described in 3b).

-   34a″) Y and Y′ are equal or different     by reacting compounds of formula (I) prepared in 28. with a compound     of formula (IIIf)

wherein Y, Y′ and Act are as above defined; A is a radical of formula (IIs) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and R₃ binds the group —Y—ONO₂, R_(s) is selected in group a″), applying the same procedure described in 3b).

-   35. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIs) wherein R₃ is —OC(O)—NH—R_(3x) and     it binds the group —Y′—ONO₂; R₁ is —C(O)O—R_(1x) and it binds the     group —Y—ONO₂, R_(s) is selected in group a″),     can be prepared as follows: -   35a) by reacting compounds of formula (I) obtained in procedure 26.     with a compound of formula (IIIu)

wherein Y, Y′ and Act are as above defined; A is a radical of formula (IIs) wherein R₁ is —C(O)O—R_(1x) and it binds the group —Y—ONO₂, R₃ is —OH and R_(s) is selected in group a″), using the same procedure described in 29b).

-   35a″) alternatively by reacting compound of formula (I) prepared     in 29. with a compound of formula (IIIf)

wherein Y, Y′ and Act are as above defined; A is a radical of formula (IIs) wherein R₁ is —H, R₃ is —OC(O)—NH—R_(3x) and it binds the group —Y—ONO₂, R_(s) is selected in group a″), applying the same procedure described in 3b).

-   36. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′ can be 0 or 1; with the proviso that s′ is 1 when A is the     radical (IIs) and (IIs) is as defined in iii) below reported, -   s″, m, m′, m″, are 0 -   Y and Y′ when presents are equal and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —COOH and R_(a) is selected from     R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —COOH and R_(c) is selected from     R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein     R_(x)—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) (s′ is 1) wherein R₁ is —H, R₃ is —OC(O) and R_(s) is     selected from R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)—; both R₃ and R_(s) bind a group —Y—ONO₂ or a     —Y′—ONO₂; -   vi) (IIs) (s′ is 0) wherein R₁ is —H, R₃ is —OC(O) and R₃ binds a     group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     —OH;     v) (IIu) wherein R₁ is —H, R₂ is —COOH, a is 1; b is 0 or 1; and     R_(x) is R_(xx)—C(O)— and R_(x) binds a group —Y—ONO₂;     can be prepared as follows: -   36a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 36., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), are as defined in 36.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   36b) by reacting a compound of formula A with a compound of formula     (IIIa)     A+Act(O)C—Y—ONO₂  (IIIe)     wherein Act and Y are as above defined and A has the following     meanings: -   i′) a radical of formula (IIa) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is     —COOH and R_(a) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   ii′) a radical of formula (IIc) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is     —COOH and R_(c) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iii′) a radical of formula (IIs) wherein R₁ is —C(O)OC(CH₃)₃, R₃ is     —OH and R_(s) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iv′) a radical of formula (IIs) wherein R₁ is —C(O)OC(CH₃)₃, R₃ is     —OH; R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   v′) a radical of formula (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is     —COOH, a is 1; b is 0 or 1 and R_(x) is —H;     following the same procedure described in 1b′) using a ratio     A/(IIIe) 1:1 or 1:2 for s′ equal to 1. -   37. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′ can be 0 or 1; with the proviso that s′ is 1 when A is the     radical (IIs) and (IIs) is as defined in iii), -   s″, m, m′, m″, are 0 -   Y and Y′, when present are equal and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —COOH and R_(a) is selected from     R_(bx)—OC(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —COOH and R_(c) is selected from     R_(bx)—OC(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) (s′ is 1) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and     R_(s) is selected from R_(bx)—OC(O)—S—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— both R₃ and R_(s) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   vi) (IIs) (s′ is 0) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and R₃     binds a group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     —OH; -   v) (IIu) wherein R₁ is —H, R₂ is —COOH, a is 1; b is 0 or 1; and     R_(x) is R_(xx)—OC(O)— and R_(x) binds a group —Y—ONO₂;     can be prepared as follows: -   37a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 37., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), are as defined in 37.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   37b) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act(O)C—O—Y—ONO₂  (IIIf)     wherein Act and Y are as above defined and A has the same meanings     described in 36b);     following the same procedure described in 3b) using a ratio A/(IIIf)     1:1 or 1:2 for s′ equal to 1. -   38. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′ can be 0 or 1; with the proviso that s′ is 1 when A is the     radical (IIs) and (IIs) is as defined in iii), -   s″, m, m′, m″, are 0 -   Y and Y′, when presents, are equal and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —COOH and R_(a) is selected from     R_(bx)—NH(O)C—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH—C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —COOH and R_(c) is selected from     R_(bx)—NH(O)C—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) (s′ is 1) wherein R₁ is —H, R₃ is —OC(O)—NH—R_(3x) and     R_(s) is selected from R_(bx)—NH(O)C—S—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH—C(O)— both R_(s) and R_(s) bind a group —Y—ONO₂ or a     group —Y′—ONO₂; -   vi) (IIs) (s′ is 0) wherein R₁ is —H, R₃ is R₃ is —OC(O)—NH—R_(3x)     and R₃ binds a group —Y—ONO₂; R_(s) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; -   v) (IIu) wherein R₁ is —H, R₂ is —COOH, a is 1; b is 0 or 1; and     R_(x) is R_(xx)—NHC(O)— and R_(x) binds a group —Y—ONO₂;     can be prepared as follows: -   38a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 38., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), are as defined in 38.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   38b) by reacting a compound of formula A with a compound of formula     (IIIu)     A+Act(O)C—NH—Y—ONO₂  (IIIu)     wherein Act and Y are as above defined and A has the same meanings     described in 36b);     following the same procedure described in 29. using a ratio A/(IIIu)     1:1 or 1:2 for s′ equal to 1. -   39. The compounds of general formula (I) wherein: -   s and a′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y′—ONO₂; and R_(a) is selected from R_(bx)—C(O)—S—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y′—ONO₂; R_(c) is selected from R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)R_(3x) and R₃ binds a group     —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(g) binds a group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)O—R_(2x), R₂ binds a group     —Y′—ONO₂; a is 1; b is 0 or 1; and R_(x) is R_(xx)—C(O)— and R_(x)     binds a group —Y—ONO₂;     can be prepared as follows: -   39a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 39., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), as defined in 39.; R₁ is —C(O)OC(CH₃)₃ with     anhydrous or aqueous organic or inorganic acid to hydrolyze the —BOC     protective groups following procedure well known in the literature. -   39b) by reacting a compound of formula (I) obtained in 36b) with a     compound of formula (IIIi)

wherein Y and Y′ are as above defined and in formula (I) A is a radical of formula (IIa), (IIc), (IIs) or (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R₃, R_(a), R_(c) R_(x) a and b are as above defined in 39.; R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedure described in 8b).

-   40. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y′—ONO₂; and R_(a) is selected from R_(bx)—OC(O)—S—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y′—ONO₂; R_(c) is selected from R_(bx)—OC(O)—S—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and R₃ binds a     group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, R_(g) is     R_(gx)—O—, and R_(s) binds a group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)O—R_(2x), R₂ binds a group     —Y′—ONO₂; a is 1; b is 0 or 1 and R_(x) is R_(xx)—OC(O)— and R_(x)     binds a group —Y—ONO₂;     can be prepared as follows: -   40a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined, in 40., A is a radical of     formula (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a),     R_(c), R_(s), R_(g) and R_(x), are as defined in 40.; R₁ is     —C(O)OC(CH₃)₃ with anhydrous or aqueous organic or inorganic acid to     hydrolyze the —BOC protective groups following procedure well known     in the literature. -   40b) by reacting a compound of formula (I) obtained in 37b) with a     compound of formula (IIIi)

wherein Y and Y′ are as above defined and in formula (I) A is a radical of formula (IIa), (IIc), (IIs) or (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R₃, R_(a), R_(c) R_(x) a and b are as above defined in 40., R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedure described in 8b).

-   41. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y′—ONO₂; and R_(a) is selected from R_(bx)—NH(O)C—S—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH—C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y′—ONO₂; R_(c) is selected from R_(bx)—NH(O)C—S—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)—NH—R_(3x) and R₃ binds a     group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     R_(gx)—O—, and R_(s) binds a group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)O—R_(2x), R₂ binds a group     —Y′—ONO₂; a is 1; b is 0 or 1 and R_(x) is R_(xx)—NHC(O)— and R_(x)     binds a group —Y—ONO₂;     can be prepared as follows: -   41a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 41., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), are as defined in 41.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   41b) by reacting a compound of formula (I) obtained in 38b) with a     compound of formula (IIIi)

wherein Y and Y′ are as above defined and in formula (I) A is a radical of formula (IIa), (IIc), (IIs) or (IIu) wherein R₁ is C(O)OC(CH₃)₃, R₂ is —COOH, R₃, R_(a), R_(c) R_(x) a and b are as above defined in 41., R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedure described in 8b).

-   42. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y′—ONO₂; and R_(a) is     selected from R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein is R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y′—ONO₂; R_(c) is selected     free R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)R_(3x) and R₃ binds a group     —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and R_(s) binds a group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y′—ONO₂; a is 1; b is 0 or     1 and R_(x) is R_(xx)—C(O)— and R_(x) binds a group —Y—ONO₂;     can be prepared as follows: -   42a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined, in 42., A is a radical of     formula (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a),     R_(c), R_(s), R_(g) and R_(x), are as defined in 42.; R₁ is     —C(O)OC(CH₃)₃ with anhydrous or aqueous organic or inorganic acid to     hydrolyze the —BOC protective groups following procedure well known     in the literature. -   42b) by reacting a compound of formula (I) obtained in 36b) with a     compound of formula (IIIo)

wherein Y and Y′ are as above defined, W₃ is as above defined and in formula (I) A is a radical of formula (IIa), (IIc), (IIs) or (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R₃, R_(a), R_(c) R_(x) a and b are as above defined in 42., R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedure described in 7b).

-   43. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y′—ONO₂; and R_(a) is     selected from R_(bx)—OC(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂—C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and R₂ binds a group —Y′—ONO₂; R_(c) is selected from     R_(bx)—OC(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and R₃ binds a     group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     R_(gxx)—NH— or R_(gxx)—N(CH₃)— and R_(s) binds a group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)NHR_(2xx)     and R₂ binds a group —Y′—ONO₂; a is 1; b is 0 or 1 and R_(x) is     R_(xx)—OC(O)— and R_(x) binds a group —Y—ONO₂;     can be prepared as follows: -   43a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 43., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), are as defined, an 43.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   43b) by reacting a compound of formula (I) obtained in 37b) with a     compound of formula (IIIo)

wherein Y and Y′ are as above defined, W₃ is as above defined and in formula (I) A is a radical of formula (IIa), (IIc), (IIs) or (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R₃, R_(a), R_(c) R_(x) a and b are as above defined in 43., R_(g) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedure described in 7b).

-   44. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y′—ONO₂; R_(a) is selected     from R_(bx)—NH(O)C—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—, 4-(R_(x)O)-3,5-R_(xx)NH—C(O)— and R_(a) binds     a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y′—ONO₂; R_(c) is selected     from R_(bx)—NH(O)C—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)—NH—R_(3x) and R₃ binds a     group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     R_(gxx)—NH— or R_(gxx)—N(CH₃)— and R_(s) binds a group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) R₂ binds a group —Y′—ONO₂; a is 1; b is 0 or 1;     and R_(x) is R_(xx)—NHC(O)— and R_(x) binds a group —Y—ONO₂;     can be prepared as follows: -   44a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 44., A is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a), R_(c),     R_(s), R_(g) and R_(x), are as defined in 44.; R₁ is C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   44b) by reacting a compound of formula (I) obtained in 38b) with a     compound of formula (IIIo)

wherein Y and Y′ are as above defined, W₃ is as above defined and in formula (I) A is a radical of formula (IIa), (IIc), (IIs) or (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R₃, R_(a), R_(c), R_(x) a and b are as above defined in 44., R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedure described in 7b).

-   45. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y—ONO₂; and R_(a) is selected from HS—CH₂—, R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y—ONO₂; and R_(a) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iii) (IIs) wherein R₁ is —H, R₃ is —H; R_(s) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and R_(s) binds a group —Y—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)OR_(2x), R₂ binds a group     —Y—ONO₂; a is 1; b is 0 or 1 and R_(x) is —H;     can be prepared as follows: -   45a) by reacting a compound of formula (VIIa)     A_(3a)-Y′—ONO₂  (VIIa)     wherein Y is as above defined and A_(3a) is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein R₂, a, b and R_(s) are as     defined in 45.; R₁ is —C(O)OC(CH₃)₃; -   in formula (IIs) R₃ is equal to R_(3a) wherein R_(3a) is —OTrt,     wherein Trt is the trityl protecting group; in formula (IIa) and     (IIc) R_(a) and R_(c) have the meanings: Trt-S—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(xa)     is -Trt, the trityl protecting group or the dimethyltertbutylsilyl     group; -   in formula (IIu) R_(x) is equal to R_(xa), wherein R_(xa) is as     above defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC and the other protective groups following procedure well known     in the literature. -   45b) by reacting a compound of formula A₃ with a compound of formula     (IIIi)     A₃+HO—Y—ONO₂  (IIIi)     wherein Y is as above defined and A₃ is a radical of formula (IIa),     (IIc), (IIs) or (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, a is     as above defined in 45., R₃ is equal to R_(3a) and is —OTrt, R_(a)     and R_(c) are TrtS—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(xa)     is as above defined; R_(x) of formula (IIu) is equal to R_(xa) and     is as above defined; R_(s) is R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;     following the same procedure described in 8b).     Compounds A₃ are commercially available or can be prepared from     commercially available compounds by simple deprotection/protection     steps well known in the literature. -   46. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y—ONO₂; and R_(a) is     selected from HS—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y—ONO₂; and R_(a) is     selected from HS—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iii) (IIs) wherein R₁ is —H, R₃ is —H; R_(s) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and R_(s) binds a     group —Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and R₂ binds a group —Y—ONO₂; a is 1; b is 0 or 1     and R_(x) is —H; can be prepared as follows: -   46a) by reacting a compound of formula (VIIb)     A_(3b)-Y—ONO₂  (VIIb)     wherein Y is as above defined and A_(3b) is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein R₂, a, b and R_(s) are as     defined in 46.; R₁ is —C(O)OC(CH₃)₃; -   in formula (IIs) R₃ is equal to R_(3a) wherein R_(3a) is —OTrt,     wherein Trt is the trityl protecting group; in formula (IIa) and     (IIc) R_(a) and R_(c) have the meanings: Trt-S—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, O-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(xa)     is as above defined; -   In formula (IIu) R_(x) is equal to R_(xa) and is as above defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC and the other protective groups following procedure well known     in the literature. -   46b) by reacting a compound of formula A₃ defined in 45b) with a     compound of formula (IIIo)     A₃+W₃NH—Y′—ONO₂  (IIIo)     following the same procedure described in 7b). -   47. The compounds of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″, are 0 -   Y is as above defined; -   B is:

-   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y—ONO₂; and R_(a) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, O-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR₂ and R₂ binds a group     B—Y—ONO₂; and R_(c) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃), (R_(x))-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iii) (IIs) wherein R₁ is —H, R₃ is —H; R_(s) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and R_(g) binds a group B—Y—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)OR_(2x), R₂ binds a group     B—Y—ONO₂; a is 1; b is 0 or 1 and R_(x) is —H; can be prepared as     follows: -   47a) by reacting a compound of formula (VIIc)     A_(3c)-Y—ONO₂  (VIIc)     wherein Y is as above defined and A_(3c) is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein R₂, a, b and R_(s) are as     defined in 47., R₁ is —C(O)OC(CH₃)₃; -   in formula (IIs) R₃ is equal to R_(3a) wherein R_(3a) is —OTrt,     wherein Trt is the trityl protecting group; in formula (IIa) and     (IIc) R_(a) and R_(c) have the meanings: Trt-S—CH₂—, or     R_(x3)O—CH₂—, R_(x3)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(xa)     is above defined; -   In formula (IIu) R_(x) is equal to R_(xa) and is as above defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC and the other protective groups following procedure well known     in the literature. -   47b) compound (VIIc) can be prepared by reacting a compound of     formula A₃ defined in 45b) with a compound of formula (IIIg) or     (IIIn) depending on the meaning of B     A₃+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     A₃+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     following the same procedure described in 4b) or 6b). -   48. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —C(O)R_(1x), and R₁ binds a group Y—ONO₂; R₂     is —COOH; and R_(a) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   ii) (IIc) wherein R₁ is —C(O)R_(1x), and R₁ binds a group Y—ONO₂; R₂     is —COOH; and R_(a) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iii) (IIs) wherein R₁ is —C(O)—R_(1x) and R₁ binds a group Y—ONO₂;     R₃ is —H; R_(s) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   v) (IIu) wherein and R₁ binds a group —Y—ONO₂; R₂ is —COOH, a is 1,     b is 0; R_(x) is —H;     can be prepared as follows: -   48a) by reacting a compound of formula (VIId)     A_(4a)-Y—ONO₂  (VIId)     wherein Y, is as above defined and A_(4a) is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₁, R₂, a, b and R_(s) are as     defined in 48.; in formula (IIs) R₃ is R_(3a) and is —OTrt; in     formula (IIa) and (IIc) R_(a) and R_(c) are TrtS—CH₂—, or     R_(x)O—CH₂—, R_(xa)O—CH(CH₃)—, (R_(xa)O)-p-C₆H₄—CH₂—,     4-(R_(xa)O)-3,5-diiodobenzyl-4-(R_(xa)O)-3-nitrobenzyl- wherein     R_(xa) is -Trt or the group dimethyl-tert-butylsilyl; R_(x) of     formula (IIu) is H or R_(xa) wherein R_(xa) is as above defined; -   with anhydrous or aqueous organic or inorganic acid to remove the     protective groups following procedure well known in the literature. -   48b) compound (VIId) are prepared by reacting a compound of formula     A₄ with a compound of formula (IIIe)     A₄+Act-C(O)—Y—ONO₂  (IIIe)     Wherein Act and Y are as above defined, A₄ is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein R₁ is —H, R₂ is —COOH, a and b     are as above defined in 48., R₃ is R_(3a), R_(a) and R_(c) are     TrtS—CH₂—, or R_(xa)O—CH₂—, R_(xa)O—CH(CH₃)—, (R_(xa)O)-p-C₆H₄—CH₂—,     4-(R_(xa)O)-3,5-diiodobenzyl-4-(R_(xa)O)-3-nitrobenzyl- wherein     R_(xa) is -Trt or dimethyl-tert-butylsilyl; R_(x) of formula (IIu)     is H or R_(xa) wherein R_(xa) is as above defined; R_(s) is     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is OH;     following the same procedure described in 1b′).     Compounds A₄ are commercially available. -   49. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   i) (IIa) wherein R₁ is —C(O)O—R_(1x), and R₁ binds a group —Y—ONO₂;     R₂ is —COOH; and R_(a) is selected from HS—CH₂—, or OR_(x)—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   ii) (IIc) wherein R₁ is —C(O)O—R_(1x), and R₁ binds a group —Y—ONO₂;     R₂ is —COOH; and R_(a) is selected from HS—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     —H; -   iii) (IIs) wherein R₁ is —C(O)—R_(1x) and R₁ binds a group Y—ONO₂;     R₃ is —H; R_(s) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   v) (IIu) wherein and R₁ binds a group —C(O)O—R_(1x) and R₁ binds a     group —Y—ONO₂; R₂ is —COOH, a is 1, b is 0 or 1 and R_(x) is —H;     can be prepared as follows: -   49a) by reacting a compound of formula (VIIf)     A_(4b)-Y—ONO₂  (VIIf)     wherein Y is as above defined and A_(4b) is a radical of formula     (IIa), (IIc), (IIs) or (IIu) wherein; R₁, R₂, a, b and R_(s) are as     defined in 49.; R₃ is R_(3a), R_(a) and R_(c) are TrtS—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(xa)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(xa)O)-3-nitrobenzyl- wherein     R_(xa) is -Trt or dimethyltert-butyl silyl, R_(x) of formula (IIu)     is H or R_(xa) wherein R_(xa) is as above defined; -   with anhydrous or aqueous organic or inorganic acid to remove the     Trityl or dimethyltert-butyl silyl protective groups following     procedure well known in the literature. -   49b) by reacting a compound of formula A₄ with a compound of formula     (IIIf) or (IIIi)     A₄+Act-C(O)O—Y—ONO₂  (IIf)     A₄+HO—Y—ONO₂  (IIIi)     Wherein Act and Y are as above defined, A₄ is as defined in 48b),     following the same procedure described in 3b). -   50. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —C(O)O, and R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, both R₂ and R_(a) bind a group —Y—ONO₂     or a group —Y′—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is —C(O)O, and R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, both R₂ and R_(c) bind a group —Y—ONO₂     or a group —Y′—ONO₂;     can be prepared as follows: -   50a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 50., A is a radical of formula     (IIa), (IIc), wherein; R₂, R_(a), R_(c), are as defined in 50.; R₁     is —C(O)OC(CH₃)₃ with anhydrous or aqueous organic or inorganic acid     to hydrolyze the —BOC protective groups following procedure well     known in the literature. -   50b) by reacting a compound of formula A with a compound of formula     (IIIi)     A+HO—Y—ONO₂  (IIIi)     wherein Y is as above defined and A is a radical of formula (IIa),     (IIc) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R_(a) and R_(c) are     selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;     following the same procedure described in 8b) using a ratio A/(IIIi)     1:2 -   51. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal and as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and both R₂ and R_(a) bind a group —Y—ONO₂ or a     group —Y′—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)— and     R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and both R₂ and R_(c) bind a group —Y—ONO₂ or a     group —Y′—ONO₂;     can be prepared as follows: -   51a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 51., A is a radical of formula     (IIa), (IIc), wherein R₂, R_(a), R_(c), are as defined in 51., R₁ is     —C(O)OC(CH₃)₃ with anhydrous or aqueous organic or inorganic acid to     hydrolyze the —BOC protective groups following procedure well known     in the literature. -   51b) by reacting a compound of formula A with a compound of formula     (IIIo)     A+W₃NH—Y—ONO₂  (IIIo)     wherein Y is as above defined, W₃ is as above defined and A is a     radical of formula (IIa), (IIc) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is     —COOH, R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     —OH;     following the same procedure described in 7b) using a ratio A/(IIIo)     1:2. -   52. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   m and m′ are equal to 1; -   m″ and s″ are 0 -   B is:

-   Y and Y′ are equal and are as above defined; -   A is selected among (IIa) and (IIc) wherein R₁ is —H and R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂ or —B′—Y′—ONO₂; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) and R_(c) bind one of the groups —B—Y—ONO₂ or —B′—Y′—ONO₂;     Can be prepared as follows: -   52a) by reacting a compound of formula (I) wherein B, s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 52., A is a radical of     formula (IIa) or (IIc) wherein R₁ is —C(O)OC(CH₃)₃; R₂, R_(a) and     R_(c) as defined in 52., -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   52b) by reacting a compound of formula A with a compound of formula     (IIIg)     A+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     wherein Y is as above defined and A is selected from (IIa) or (IIc)     wherein R₂ is —COOH and R₁ is —C(O)O(CH₃)₃; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;     using a ratio A/(IIIg) 1:2 and applying the procedure described on     4b). -   33. One compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   m and m′ are equal to 1; -   m″ and s″ are 0 -   B is:

-   Y and Y′ are equal and are as above defined; -   A is selected among (IIa) and (IIc) wherein R₁ is —H and R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂ or —B′—Y′—ONO₂; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) and R_(c) bind one of the groups —B—Y—ONO₂ or —B′—Y′—ONO₂;     Can be prepared as follows: -   53a) by reacting a compound of formula (I) wherein B, s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 53., A is a radical of     formula (IIa) or (IIc) wherein R₁ is —C(O)OC(CH₃)₃; -   R₂, R_(a) and R_(c) are as defined in 53., -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   53b) by reacting a compound of formula A with a compound of formula     (IIIn)     A+Hal-W₁—O(O)C—B—Y—ONO₂  (IIIn)     wherein Y is as above defined and A is selected from (IIa) or (IIc)     wherein R₂ is —COOH and R₁ is —C(O)O(CH₃)₃; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;     Using a ratio A/(IIIn) 1:2 and applying the procedure described in     6b). -   54. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′, m″, are 0 -   Y, Y′ and Y″ are as above defined with the proviso that Y is equal     to Y′ -   A is a radical of formula (IIa) or (IIc) wherein R₁ is —C(O)—R_(1x)     and it binds the group —Y″—ONO₂, R₂—C(O)OR_(2x) and it binds the     group Y—ONO₂ or Y′—ONO₂; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O—, and     R_(a) and R_(c) bind one of the groups —Y—ONO₂ or —Y′—ONO₂;     can be prepared as follows: -   54a) by reacting a compound of formula (I) prepared as described in     49.     with a compound of formula (IIIe):

wherein in formula (I) Y and Y′ are equal and A is a radical of formula (IIa) or (IIc) wherein R₁ is —H; R₂, R_(a) and R_(c) are as defined in 54., following the same procedure described in 1b′).

-   55. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′, m″, are 0 -   Y, Y′ and Y″ are as above defined with the proviso that Y is equal     to Y′ -   A is a radical of formula (IIa) or (IIc) wherein —C(O)O—R_(1x) and     it binds the group —Y″—ONO₂, R₂ is —C(O)OR_(2x) and it binds the     group —Y—ONO₂ or —Y′—ONO₂; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O—, and     R_(a) and R_(c) bind one of the groups —Y—ONO₂ or —Y′—ONO₂;     can be prepared as follows: -   55a) by reacting a compound of formula (I) prepared as described in     49.     with a compound of formula (IIIf):

wherein in formula (I) Y and Y′ are equal and A has been already defined in 54.; following the same procedure described in 3b).

-   56. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′, m″, are 0 -   Y, Y′ and Y″ are as above defined with the proviso that Y is equal     to Y′ -   A is a radical of formula (IIa) or (IIc) wherein R₁ is —C(O)—R_(1x)     and it binds the group —Y″—ONO₂, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₂)R_(2xx) and it binds the group —Y—ONO₂ or —Y′—ONO₂; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)NH— or     R_(gx)—N(CH₃)— and R_(a) and R_(c) bind one of the groups —Y—ONO₂ or     —Y′—ONO₂;     can be prepared as follows: -   56a) by reacting a compound of formula (I) prepared as described in     51.     with a compound of formula (IIIe):

wherein in formula (I) Y and Y′ are equal and A is a radical of formula (IIa) or (IIc) wherein R₁ is —H; R₂, R_(a) and R_(c) are as defined in 56., following the same procedure described in 1b′).

-   57. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′, m″, are 0 -   Y, Y′ and Y″ are as above defined with the proviso that Y is equal     to Y′ -   A is a radical of formula (IIa) or (IIc) wherein R₁ is —C(O)O—R_(1x)     and it binds the group —Y″—ONO₂, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and it binds the group —Y—ONO₂ or —Y′—ONO₂; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)NH— or     R_(gx)N(CH₃)— and R_(a) and R_(c) bind one of the groups —Y—ONO₂ or     —Y′—ONO₂;     can be prepared as follows: -   57a) by reacting a compound of formula (I) prepared as described in     51.     with a compound of formula (IIIf):

wherein in formula (I) Y and Y′ are equal and A has been already defined in 56., following she same procedure described in 3b).

-   58. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m and m′ are equal to 1 -   m″ is 0; -   B is:

-   Y, Y′ and Y″ are as above defined with the proviso that Y is equal     to Y′ -   A is a radical of formula (IIa) or (IIc) wherein R₁ is —C(O)—R_(1x)     and it binds the group —Y″—ONO₂, R₂ is —C(O)OR_(2x) and it binds the     group B—Y—ONO₂ or B—Y′—ONO₂ wherein B—Y—ONO₂ or B—Y′—ONO₂ are equal; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O—, and     R_(a) and R_(c) bind one of the groups B—Y—ONO₂ or B—Y′—ONO₂ wherein     in B—Y—ONO₂ or B—Y′—ONO₂ are equal;     can be prepared as follows: -   58a) by reacting a compound of formula (I) prepared as described     in 52. if B is:

or prepared in 53. if B is:

with a compound of formula (IIIe):

wherein in formula (I) B, Y and Y′ are as defined in 58.; and A is a radical of formula (IIa) or (IIc) wherein R₁ is —H; R₂, R_(a) and R_(c) are as defined in 58., following the same procedure described in 1b′).

-   59. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m and m′ are equal to 1; -   m″ is 0 -   B is:

-   Y, Y′ and Y″ are as above defined with the proviso that Y is equal     to Y′ -   A is a radical of formula (IIa) or (IIc) wherein R₁ is —C(O)O—R_(1x)     and it binds the group —Y″—ONO₂, R₂ is —C(O)OR_(2x) and it binds the     group B—Y—ONO₂ or B—Y′—ONO₂ wherein B—Y—ONO₂ or B—Y′—ONO₂ are equal; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) and R_(c) bind one of the groups B—Y—ONO₂ or B—Y′—ONO₂ wherein     B—Y—ONO₂ or B—Y′—ONO₂ are equal;     can be prepared as follows: -   59a) by reacting a compound of formula (I) prepared as described     in 52. if B is:

-   or prepared in 53. if B is:

with a compound of formula (IIIf):

wherein in formula (I) B, Y and Y′ are as defined in 59.; A is a radical of formula (IIa) or (IIc) wherein R₁ is —H; R₂, R_(a) and R_(c) are as defined in 59., following the same procedure described in 3b).

-   60. The compounds of general formula (I) wherein: -   s, is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa) and (IIc) wherein R₁ is —C(O)—R_(1x) and     binds a group —Y—ONO₂, R₂ is —COOH; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; can be     prepared as follows: -   60a) by reacting a compound of formula A with a compound of formula     (IIIe)     A+Act-(O)C—Y—ONO₂  (IIIe)     wherein Y is as above defined and A is a commercially available     compound of formula (IIa) or (IIc) wherein R₂ is —COOH and R₁ is —H; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;     applying the procedure described in 1b′). -   61. The compounds of general formula (I) wherein: -   s, is equal to 1; -   s′, s″, m, m′ and m″ are 0; -   Y is as above defined; -   A is selected among (IIa) and (IIc) wherein R₁ is —C(O)O—R_(1x) and     binds a group —Y—ONO₂, R₂ is —COOH; -   R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; can be     prepared as follows: -   61a) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act-(O)C—O—Y—ONO₂  (IIIf)     wherein Y is as above defined and A is as defined in 60a) applying     the procedure described in 3b). -   62. Alternatively compounds (I) described in 54. can be prepared     starting from compounds (I) prepared as described in 60. and     compounds (IIIi) applying the same procedure described in 8b) using     a ratio (I)/(IIIi) 1:2. In this case Y′ and Y″ are equal.

-   63. Alternatively compounds (I) described in 55. can be prepared     starting from compounds (I) prepared as described in 61. and     compounds (IIIi) applying the same procedure described in 8b) using     a ratio (I)/(IIIi) 1:2. In this case Y′ and Y″ are equal.

-   64. Alternatively compounds (I) described in 56. can be prepared     starting from compounds (I) prepared as described in 60. and     compounds (IIIo) applying the same procedure described in 7b) using     a ratio (I)/(IIIo) 1:2. In this case Y′ and Y′ are equal.

-   65. Alternatively compounds (I) described in 57. can be prepared     starting from compounds (I) prepared as described in 61. and     compounds (IIIo) applying the same procedure described in 7b) using     a ratio (I)/(IIIo) 1:2. In this case Y′ and Y″ are equal.

-   66. Alternatively compounds (I) described in 58. can be prepared     starting from compounds (I) prepared as described in 60. and     compounds (IIIg) or (IIIn) depending on the meaning of B, and     applying the same procedure described in 4b) or 6b) using a ratio     (I)/(IIIg) or (I)/(IIIn) 1:2. In this case Y′ and Y″ are equal.

-   67. Alternatively compounds (I) described in 59. can be prepared     starting from compounds (I) prepared as described in 61. and     compounds (IIIg) or (IIIn) depending on the meaning of B, and     applying the same procedure described in 4b) or 6b) using a ratio     (I)/(IIIg) or (I)/(IIIn) 1:2. In this case Y′ and Y″ are equal.

-   68. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y—ONO₂; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y—ONO₂; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; can be     prepared as follows: -   68a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 68., A is a radical of formula     (IIa), (IIc), wherein R₂ is as above defined in 68.; R₁ is     —C(O)OC(CH₃)₃; R_(a) and R_(c) are R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     tert-butyl esters and the —BOC protective groups following procedure     well known in the literature. -   68b) by reacting a compound of formula A with a compound of formula     (IIIi)     A+HO—Y—ONO₂  (IIIi)     wherein Y is as above defined and A is a compound of formula (IIa)     or (IIc) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R_(a) and R_(c)     are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is —C(O)OC(CH₃)₃; -   following the same procedure described in 8b). Compounds A are     commercially available. -   69. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is a radical of formula -   (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and R₂ binds a group —Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; or -   (IIc) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and R₂ binds a group —Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; can be prepared as follows: -   69a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 69., A is a radical of formula     (IIa), (IIc), wherein R₂ is as above defined in 69.; R₁ is     —C(O)OC(CH₃)₃); R_(a) and R_(c) are R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     tert-butyl esters and the —BOC protective groups following procedure     well known in the literature. -   69b) by reacting a compound of formula A with a compound of formula     (IIIo)     A+W₃NH—Y—ONO₂  (IIIo)     wherein Y is as above defined, W₃ is as above defined and A is as     defined in 68b),     following the sane procedure described in 7b). -   70. The compounds of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″, are 0 -   Y is as above defined; -   B is:

-   A is a radical selected among: -   (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —B—Y—ONO₂; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —B—Y—ONO₂; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; can be     prepared as follows: -   70a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, B, Y, Y′, Y″ are as above defined in 70., A is a radical of     formula (IIa), (IIc), wherein R₂ is as above defined in 70.; R₁ is     —C(O)OC(CH₃)₃); R_(a) and R_(c) are R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     tert-butyl esters and the —BOC protective groups following procedure     well known in the literature. -   70b) by reacting a compound of formula A with a compound of formula     (IIIg) or (IIIn) depending on the meaning of B     A+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     A+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     wherein Y, Hal, W₁ are as above defined and A is as defined in 68b),     following the same procedures described in 4b) or 6b). -   71. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —COOH; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and R_(g) binds a group —Y—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is —COOH; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and R_(c) binds a group —Y—ONO₂;     can be prepared as follows: -   71a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 71., A is a radical of formula     (IIa), (IIc), wherein R_(a) and R_(c) are as above defined in 71.;     R₁ is —C(O)OC(CH₃)₃; R₂ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     tert-butyl esters and the —BOC protective groups following procedure     well known in the literature. -   68b) by reacting a compound of formula A with a compound of formula     (IIIi)     A+HO—Y—ONO₂  (IIIi)     wherein Y is as above defined and A is a radical of formula (IIa),     (IIc) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —C(O)OC(CH₃)₃, R_(a) and     R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;     following the same procedure described in 8b). -   Compounds A are commercially available. -   72. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —COOH; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and R_(a) binds a     group —Y—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is —COOH; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and R_(c) binds a     group —Y—ONO₂;     can be prepared as follows: -   72a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 72., A is a radical of formula     (IIa), (IIc), wherein R_(a) and R_(c) are as above defined in 71.;     R₁ is —C(O)OC(CH₃)₃; R₂ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     tert-butyl esters and the —BOC protective groups following procedure     well known in the literature. -   72b) by reacting a compound of formula A with a compound of formula     (IIIo):     A+W₃NH—Y—ONO₂  (IIIo)     wherein Y and W₃ are as above defined and A is as defined in 71b)     following the same procedure described in 7b). -   73. One compounds of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″, are 0 -   Y is as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —COOH; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and R_(a) binds a group —B—Y—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is —COOH; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and R_(c) binds a group B—Y—ONO₂;     can be prepared as follows: -   73a) by reacting a compound of formula (I) wherein s, s′, s″, m, m′,     m″, B, Y, Y′, Y″ are as above defined in 73., A is a radical of     formula (IIa), (IIc), wherein R_(a) and R_(c) are as above defined     in 71.; R₁—C(O)OC(CH₃)₃); R₂ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     tert-butyl esters and the —BOC protective groups following procedure     well known in the literature. -   73b) by reacting a compound of formula A with a compound of formula     (IIIg) or (IIIn) depending on the meaning of B     A+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     A+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     wherein Y, Hal, W₁ are as above defined and A is as defined in 71b),     following the same procedures described in 4b) or 6b). -   74. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(s) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH;     can be prepared as follows: -   74a) by reacting a compound of formula (I) prepared as described     in 68. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedures described in 1b′).

-   75. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; wherein R_(g) is —OH; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH;     can be prepared as follows: -   75a) by reacting a compound of formula (I) prepared as described     in 68. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is as defined in 74a); following the same procedures described in 3b).

-   76. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R₁ and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂;     R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₂)R_(2xx) and binds a group —Y—ONO₂;     R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; can be     prepared as follows: -   76a) by reacting a compound of formula (I) prepared as described     in 69. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; following the same procedures described in 1b′).

-   77. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂;     R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₂)R_(2xx) and binds a group —Y—ONO₂;     R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, -   77a) by reacting a compound of formula (I) prepared as described     in 69. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is as above defined in 76., following the same procedures described in 3b).

-   78. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; can be prepared as follows: -   78a) by reacting a compound of formula (I) prepared as described     in 70. with a compound of formula (IIIe):

wherein Act, B, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds a group B—Y—ONO₂; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH;

-   79. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is —OH; can be prepared as follows: -   79a) by reacting a compound of formula (I) prepared as described     in 70. with a compound of formula (IIIf):

wherein Act, B, Y and Y′ are as above defined and A is as defined in 78a), following the same procedures described in 3b).

-   80. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) binds a group —Y—ONO₂ -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(gx) is R_(gx)—O—, and     R_(c) binds a group —Y—ONO₂;     can be prepared as follows: -   80a) by reacting a compound, of formula (I) prepared as described     in 71. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —COOH; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and R_(a) and R_(c) bind a group —Y—ONO₂ following the same procedures described in 1b′).

-   81. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and it binds a group —Y′—ONO₂; R₂     is —COOH; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) binds a group —Y—ONO₂ -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(c) binds a group —Y—ONO₂;     can be prepared as follows: -   81a) by reacting a compound of formula (I) prepared as described     in 71. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —COOH; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O— and R_(a) and R_(c) bind a group —Y—ONO₂, following the same procedures described in 3b).

-   82. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂; R₂     is —COOH; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and R_(a) binds a group —Y′—ONO₂ -   (IIc) wherein R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂; R₂     is —COOH; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and R_(c) binds a group —Y—ONO₂;     can be prepared as follows: -   82a) by reacting a compound of formula (I) prepared as described     in 72. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —COOH; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)—

-   and R_(a) and R_(c) bind a group —Y—ONO₂ -   following the same procedures described in 1b′). -   83. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and R_(a) binds a group —Y—ONO₂; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or     R_(gxx)—N(CH₃)— and R_(c) binds a group —Y—ONO₂;     can be prepared as follows: -   83a) by reacting a compound of formula (I) prepared as described     in 72. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is as defined in 82a), following the same procedures described in 3b).

-   84. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) binds a group —B—ONO₂; -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(c) binds a group —B—Y—ONO₂;     can be prepared as follows: -   84a) by reacting a compound of formula (I) prepared as described     in 73. with a compound of formula (IIIe):

wherein Act, B, Y and Y′ are as above defined and A is a radical of formula, (IIa), (IIc), wherein R₁ is —H, R₂ is —COOH; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O— and R_(a) and R_(c) bind a group B—Y—ONO₂, following the same procedures described in 1b′).

-   85. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —COOH; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(a) binds a group —B—Y—ONO₂; -   (IIc) wherein R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂; R₂     is —COOH; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O— and     R_(c) binds a group —B—Y—ONO₂;     can be prepared as follows: -   85a) by reacting a compound of formula (I) prepared as described     in 73. with a compound of formula (IIIf):

wherein Act, B, Y and Y′ are as above defined and A is as defined in 84a), following the same procedures described in 3b).

-   86. The compound of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″ are equal to 0; -   Y and Y′ are equal and are as above defined; -   A is selected from (IIa), (IIc) or (IIt) wherein R₁ is —C(O)—R_(1x)     and it binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is —COOH; R_(a)     of formula (IIa) and R_(c) of formula (IIc) are R_(h)NH(CH₂)_(p)—     wherein p is an integer from 0 to 4, or R_(i)NH(═NH)NH—(CH₂)₃—, and     R_(h) and R_(i) are R_(hh)—C(O)— or R_(ii)—C(O)— and R_(a) and R_(c)     bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ is —C(O)—R_(1x) and it binds a group —Y—ONO₂ or     a group —Y′—ONO₂, R₂ is —COOH; d is 2 d′ is 1, R_(t) is —C(O)—R_(tt)     and it binds a group —Y—ONO₂ or a group —Y′—ONO₂;     can be prepared as follows: -   86a) by reacting a compound of formula A with a compound of formula     (IIIe)     A+Act-(O)C—Y—ONO₂  (IIIe)     wherein Act and Y are as above defined and A is a compound of     formula (IIa), (IIc) or (IIt) wherein R₁ is —H and R₂ is —COOH;     R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4,     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are —H;

in formula (IIt) R₁ is —H, R₂ is —COOH, d is 2 d′ is 1, R_(t) is —H; using a ratio A/(IIIe) 1:2 and applying the same procedure described in 1b′). Compounds A are commercially available.

-   87. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ are equal and are as above defined; -   A is a radical selected from (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is     —COOH; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ is —C(O)—R_(1x) and binds a group —Y—ONO₂ or a     group —Y′—ONO₂, R₂ is —COOH; -   d is 2 d′ is 1, R_(t) is —C(O)—R_(tt) and binds a group —Y—ONO₂ or a     group —Y′—ONO₂;     can be prepared as follows. -   87a) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act-(O)C—O—Y—ONO₂  (IIIf)     wherein Act and Y are as above defined and A is as defined in 86a)     using a ratio A/(IIIf) 1:2 and applying the same procedure described     in 3b). -   88. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are equal to 0; -   Y is as above defined; -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —H, -   R₂ is —C(O)OR_(2x) and it binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are the groups     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4,     R_(i)NH(═NH)NH—(CH₂)₃—, R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —H, and R₂ is —C(O)OR_(2x) and it binds a     group —Y—ONO₂; d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   88a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H;     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 88. A is a radical of (IIa), (IIc)     or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is —CO(O)R_(2x) and bind;     R_(a) of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R₁ and R₂ are as above defined d is 2 d′ is 1,     R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   88a′) R_(a)=R_(c) selected from R_(i)NH(═NH)—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIa)     A_(5a)-Y—ONO₂  (VIIIa)     wherein Y, is as above defined; A_(5a) is a radical of formula     (IIa), (IIc) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is —CO(O)R_(2x); R_(a)     of formula (IIa) and R_(c) of formula (IIc) are     R_(ia)—NH(═NH)NH—(CH₂)₃— wherein R_(ia) is the known protective     group —Pbf (2,2,4,6,7-pentamethyl-dihydrobenzofuran-5-sulfonyl)-; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —HOC and the —Pbf protective groups following procedure well known     in the literature. -   88b) compounds described in 88a) and 88a′) can be respectively     obtained by reacting a compound of formula A or A₅ with a compound     of formula (IIIi)     A+HO—Y—ONO₂→(I)  (IIIi)     A₅+HO—Y—ONO₂→(VIIIa)  (IIIi)     wherein Y is as above defined, and: -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)OC(CH₃)₃; R₂ is —COOH; R_(a) and R_(c) are R_(h)NH(CH₂)_(p)—     wherein p as above defined and R_(h) is —C(O)OC(CH₃)₃; d and d′ are     as above defined, and R_(t) is —C(O)OC(CH₃)₃; -   A₅ is a radical of formula (IIa) or (IIc) wherein R₁ is     —C(O)OC(CH₃)₃; R₂ is —COOH; R_(a) and R_(c) are     R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is as above defined using the     same procedure described in 8b).     Compounds A and A₅ as above defined are commercially available or     can be easily obtained from commercially available compounds by     simple deprotection/protection steps as known in the literature. -   89. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″ are equal to 0; -   Y is as above defined; -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —H, -   R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and it binds a group     —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —H, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and it binds a group —Y—ONO₂; d is 2 d′ is 1,     R_(t) is —H;     can be obtained as follows: -   89a) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 89. A is a radical of formula     (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx); R_(a), R_(c), p, d, d′, R_(h)     and R_(t) are as defined in 88a) with anhydrous or aqueous organic     or inorganic acid to hydrolyze the —BOC protective groups. -   89a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIIb):     A₆-Y—ONO₂  (VIIIb)     wherein Y, is as above defined; A₆ is a radical of formula (IIa),     (IIc) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)_(2xx); R_(a) of formula (IIa) and R_(c) of formula (IIc)     are R_(ia)—NH(═NH)NH—(CH₂)₃ wherein R_(ia) is the —Pbf group as     above defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC and the —Pbf protective groups following procedure well known     in the literature. -   89b) compounds described in 89a) and 89a′) can be respectively     obtained by reacting a compound of formula A or a compound of     formula A₅ already defined in 88b) with a compound of formula (IIIo)     A+W₃NH—Y—ONO₂→(I)  (IIIo)     A₅+W₃NH—Y—ONO₂→(VIIIb)  (IIIo)     using the same procedure described in 7b). -   90. The compounds of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″ are equal to 0; -   Y is as above defined; -   B is:

-   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —H, -   R₂ is —C(O)OR_(2x) and binds a group —B—Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —H, R₂ is —C(O)OR_(2x) and it binds a group     —B—Y—ONO₂; d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   90a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) wherein B, s, s′, s″, m, m′,     m″, Y, Y′, Y″ are as above defined in 90. A is a radical of formula     (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is     —C(O)OR_(2x); B, R_(a), R_(c), p, d, d′, R_(h) and R_(t) are as     defined in 90. with anhydrous or aqueous organic or inorganic acid     to hydrolyze the —BOC protective groups. -   90a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIIc):     A_(5a)-B—Y—ONO₂  (VIIIc)     wherein B, and Y, are as above defined in 90. and A_(5a) is as     defined in 88a′) with anhydrous or aqueous organic or inorganic acid     to hydrolyze the —BOC and the —Pbf protective groups following     procedure well known in the literature. -   90b) compounds described in 90a) and 90a′) can be respectively     obtained by reacting a compound of formula A or a compound of     formula A₅ already defined in 88b) with compounds (IIIg) or (IIIn)     depending on the meaning of B, and applying the same procedure     described in 4b) or 6b):     A or A₅+Hal-W₁—OC(O)—Y—ONO₂→(I) or (VIIIc)  (IIIg)     A or A₅+Hal-W₁—OC(O)—O—Y—ONO₂→(I) or (VIIIc)  (IIIn) -   91. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)—R_(1x)     and binds a group —Y′—ONO₂, R₂ is —C(O)OR_(2x) and binds a group     —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂,     R₂ is —C(O)OR_(2x) and R₂ binds a group —Y—ONO₂; d is 2 d′ is 1,     R_(t) is —H;     can be obtained as follows: -   91a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 91. A is a radical of (IIa), (IIc)     or (IIt) wherein R₁ is —C(O)—R_(1x); R₂ is —C(O)OR_(2x); R_(a) of     formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R₁ and R₂ are as above defined d is 2 d′ is 1,     R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   91a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H: -   by reacting a compound of formula (VIIId)

wherein Y and Y′ are as above defined; A_(7a) is a radical of formula (IIa), (IIc) wherein R₁ is —C(O)—R_(1x); R₂ is —CO(O); R_(a) of formula (IIa) and R_(c) of formula (IIc) are R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is group —Pbf as already defined;

-   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   91b) R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p     is an integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) with a compound of formula     (IIIe)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(h)NH(CH₂)_(p)— wherein p as above defined and R_(h) is —C(O)OC(CH₃)₃; d and d′ are as above defined, and R_(t) is —C(O)OC(CH₃)₃; using the same procedure described in 1b′).

-   91b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIIe) with a compound of formula     (IIIe):

wherein Y and Y′ are as above defined and A₇ is a radical of formula (IIa), (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is group —Pbf as above defined; using the same procedure described in 1b′).

-   91c) compounds described in 91b) and 91b′) can be respectively     prepared by deprotecting the Fmoc group of a compound of formula     (VIIIf₁) or (VIIIf₂)     A_(8a)-Y—ONO₂→(I)  (VIIIf₁)     A_(8b)-Y—ONO₂→(VIIIe)  (VIIIf₂)     wherein Y is as above defined and: -   A_(8a) is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     the Fmoc protective group; R₂ is —C(O)OR_(2x) and binds the group     —Y—ONO₂; R_(a) and R_(c) are R_(h)NH(CH₂)_(p)— wherein p is as above     defined and R_(h) is —C(O)OC(CH₃)₃, -   A_(8b) is a radical of formula (IIa) or (IIc) wherein R₁ is the Fmoc     protective group; R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂;     R_(a) and R_(c) are R_(ia)NH(═NH)NH—(CH₂)₃—, wherein R_(ia) is the     —Pbf group as above defined; -   91d) compound of formula (VIIIf₁) or (VIIIf₂) are prepared by     reacting a compound of formula A_(9a) or A_(9b) with composed (IIIi)     using the same procedure described in 8b)     A_(ga)+HO—Y—ONO₂→(VIIIf₁)  (IIIi)     A_(gb)+HO—Y—ONO₂→(VIIIf₂)  (IIIi)     wherein Y is as above defined and: -   A_(9a) is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     the Fmoc protective group; R₂ is —COOH; R_(a) and R_(c) are     R_(h)NH(CH₂)_(p)— wherein p as above defined and R_(h) is     —C(O)OC(CH₃)₃; -   A_(9b) is a radical of formula (IIa) or (IIc) wherein R₁ is the Fmoc     protective group; R₂ is —COOH; R_(a) and R_(c) are     R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is the —Pbf group as     previously defined.     Compounds A_(9a) and A_(9b) are commercially available. -   92. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)—R_(1x) and it binds a group —Y′—ONO₂, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃R_(2xx) and it binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     —R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂     is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and it binds a group     —Y—ONO₂; d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   92a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 92. A is a radical of (IIa), (IIc)     or (IIt) wherein R₁ is —C(O)—R_(1x); R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx); -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R₁ and R₂ are as above defined d is 2 d′ is 1,     R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   92a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIIg)

wherein Y and Y′ are as above defined; A_(10a) is a radical of formula (IIa), (IIc) wherein R₁ R₁ is —C(O)—R_(1x); R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx);

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(ia)—NH(═NH)NH—(CH₂)₃— wherein R_(ia) is the —Pbf group -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   92b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) with a compound of formula     (IIIe)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(h)NH(CH₂)_(p)— wherein p as above defined and R_(h) is —C(O)OC(CH₃)₃; d and d′ are as above defined, and R_(t) is —C(O)OC(CH₃)₃; using the same procedure described in 1b′).

-   92b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     compound (VIIIg) is prepared by reacting a compound of formula     (VIIIh) with a compound of formula (IIIe)

wherein Y and Y′ are as above defined and A_(10a) is a radical of formula (IIa), (IIc) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(1a)—NH(═NH)NH—(CH₂)₃— wherein R_(ia) is as above defined using the same procedure described in 1b′).

-   92c) compounds described in 92b) and 92b′) can be prepared by     deprotecting the Fmoc group of a compound, of formula (VIIIi₁) or     (VIIIi₂)     A_(11a)-Y—ONO₂→(I)  (VIIIi₁)     A_(11b)-Y—ONO₂→(VIIIh)  (VIIIi₂)     wherein Y is as above defined and: -   A_(11a) is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     the Fmoc protective group; R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are     R_(h)NH(CH₂)_(p)— wherein p is as above defined and R_(h) is     —C(O)OC(CH₃)₃, -   A_(11b) is a radical of formula (IIa) or (IIc) wherein R₁ is the     Fmoc protective group; R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and binds the group —Y—ONO₂; R_(a) and R_(c) are     R_(ia)NH(═NH)NH—(CH₂)₃, wherein R_(ia) is as above defined; -   92d) compounds described on 92c) can be prepared by reacting a     compound of formula A_(9a) or a compound of formula A_(9b) defined     in 91d) with compound (IIIo) using the same procedure described in     7b)     A_(9a)+W₃NH—Y—ONO₂→(VIIIi₁)  (IIIo)     A_(9b)+W₃NH—Y—ONO₂→(VIIIi₂)  (IIIo)     wherein Y and W₃ are as above defined. -   93. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′ and m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and binds a group —Y′—ONO₂, R₂ is —C(O)OR_(2x) and     binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃, and R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂, and     R₂ is —C(O)OR_(2x) and binds a group —Y—ONO₂; d is 2 d′ is 1, R_(t)     is —H;     can be obtained as follows: -   93a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 93. A is a radical of formula     (IIa), (IIc) or (IIt) wherein R₁ is —C(O)O—R_(1x); R₂ is     —C(O)OR_(2x); -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R₁ and R₂ are as above defined d is 2 d′ is 1,     R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   93a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIIj)

wherein Y and Y′ are as above defined; A_(11a) is a radical of formula (IIa), (IIc) wherein R₁ is —C(O)O—R_(1x); R₂ is —C(O)OR_(2x) R_(a) of formula (IIa) and R_(c) of formula (IIc) are R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is as already defined;

-   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   93b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) with a compound of formula     (IIIf)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) already defined in 91b) and obtained as described in 91c), using the same procedure described in 3b).

-   93b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i)—H:     Compound of formula (VIIIj) are prepared by reacting a compound of     formula (VIIIe) already defined in 91b′) and obtained as described     in 91c) with a compound of formula (IIIf)

wherein A₈, Y and Y′ are as above defined, using the same procedure described in 3b).

-   94. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′ and m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and binds a group —Y′—ONO₂, R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂, and     R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group     —Y—ONO₂; d is 2 d′ is 1 R_(t) is —H;     can be obtained as follows: -   94a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H;     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 94. A is a radical of (IIa), (IIc)     or (IIt) wherein R₁ is —C(O)O—R_(1x); R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx); -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R₁ and R₂ are as above defined d is 2 d′ is 1,     R_(t) as —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   94a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     by reacting a compound of formula (VIIIk)

wherein Y and Y′ are as above defined; A_(12a) is a radical of formula (IIa), (IIc) wherein R₁ is —C(O)O—R_(1x), R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx);

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is group —Pbf -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   94b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H: -   by reacting a compound of formula (I) with a compound of formula     (IIIf)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) already defined in 92b) and obtained as described in 92c), using the same procedure described in 3b).

-   94b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is —H:     Compound (VIIIk) are prepared by reacting a compound of formula     (VIIIh) already defined in 92b′) and obtained as described in 92c)     with a compound of formula (IIIf)

wherein Y and Y′ are as above defined using the same procedure described in 3b).

-   95. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′ and m″ are equal to 0; -   Y, Y′ and Y″ are as above defined, with the proviso that Y and Y′     are equal; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁—C(O)—R_(1x) and     it binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is —C(O)OR_(2x) and     it binds a group —Y″—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)—R_(tt) and it binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     can be prepared as follows: -   95a) by reacting a compound of formula (I) with a compound of     formula (IIIi)

wherein in compounds (I), obtained as described in 86. Y and Y′ are equal and are as above defined and A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂ and R₂ is —COOH;

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)— and bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)—R_(tt) and it binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     using the same procedure described in 8b). -   96. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′ and m″ are equal to 0; -   Y, Y′ and Y″ are as above defined, with the proviso that Y and Y′     are equal; -   A is a radical of formula (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and it binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂     is —C(O)OR_(2x) and it binds a group —Y″—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt) and binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     can be prepared as follows: -   96a) by reacting a compound of formula (I) with a compound of     formula (IIIi)

wherein in compounds (I), obtained as described in 87. Y and Y′ are equal and are as above defined and A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂ and R₂ is —COOH;

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)— and bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt); and binds a group —Y—ONO₂ or a group     —Y′—ONO₂; using the same procedure described in 8b). -   97. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′ and m″ are equal to 0; -   Y, Y′ and Y″ are as above defined, and Y and Y′ are equal; -   A is a radical of formula from (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)—R_(1x) and it binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and it binds a group —Y″—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)—R_(tt) and binds a group —Y—ONO₂ or a group —Y′—ONO₂;     can be prepared as follows: -   97a) by reacting a compound of formula (I) with a compound of     formula (IIIo)

wherein in compounds (I), obtained as described in 86. Y and Y′ are equal and are as above defined and A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂ and R₂ is —COOH;

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)— and bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)—R_(tt) and binds a group —Y—ONO₂ or a group —Y′—ONO₂;     using the same procedure described in 7b). -   98. The compounds of general formula (I) wherein: -   s, s′ and s″ are equal to 1; -   m, m′ and m″ are equal to 0; -   Y, Y′ and Y″ are as above defined and Y and Y′ are equal; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y″—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt) and binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     can be prepared as follows: -   98a) by reacting a compound of formula (I) with a compound of     formula (IIIo)

wherein in compounds (I), obtained as described in 87. Y and Y′ are equal and are as above defined, W₃ is as above defined and A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂ and R₂ is —COOH;

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)— and bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt) and binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     using the same procedure described in 7b). -   99. The compounds of general formula (I) wherein: -   s, s′, s″ and m″ are equal to 1; -   m, m′ are equal to 0; -   Y, Y′ and Y″ are as above defined, with the proviso that Y and Y′     are equal; -   B is:

-   A is a radical of formula (IIa), (IIc) and (IIt) wherein R₁ is —C(O)     and binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is —C(O)OR_(2x)     and binds a group —B—Y″—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—OC(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined d is 2 d′ is 1,     R_(t) is —C(O)—R_(tt) and binds a group —Y—ONO₂ or a group —Y′—ONO₂;     can be prepared as follows: -   99a) by reacting a compound of formula (I) obtained as described in     86.

with compounds (IIIg) or (IIIn) depending on the meaning of B: (I)+Hal-W₁—OC(O)O—Y′—ONO₂  (IIIg) (I)+Hal-W₁—OC(O)—Y′—ONO₂  (IIIn) wherein in compounds (I), obtained as described in 86. Y and Y′ are equal and are as above defined and A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂ and R₂ is —COOH;

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—C(O)— and     bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)—R_(tt) and binds a group —Y—ONO₂ or a group —Y′—ONO₂;     and applying the same procedure described in 4b) or 6b). -   100. The compounds of general formula (I) wherein: -   s, s′, s″ and m″ are equal to 1; -   m, m′ are equal to 0; -   Y, Y′ and Y″ are as above defined, with the proviso that Y and Y′     are equal; -   B is:

-   A is a radical of formula (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and it binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂     is —C(O)OR_(2x) and it binds a group —B—Y″—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt) and it binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     can be prepared as follows: -   100a) by reacting a compound of formula (I) obtained as described in     87.

with compounds (IIIg) or (IIIn) depending on the meaning of B: (I)+Hal-W₁—OC(O)O—Y′—ONO₂  (IIIg) (I)+Hal-W₁—OC(O)—Y′—ONO₂  (IIIn) wherein is compounds (I) Y and Y′ are equal and are as above defined and A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂ and R₂ is —COOH;

-   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—C(O)— and bind a group —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ and R₂ are as above defined, d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt) and binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     and applying the same procedure described in 4b) or 6b). -   101. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′ and m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —H, -   R₂ is —C(O)OR_(2x) and it binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)— and R_(a) and R_(c) bind a group —Y′—ONO₂ -   in formula (IIt) R₁ is —H, and R₂ is —C(O)OR_(2x) and binds a group     —Y—ONO₂; d is 2 d′ is 1, R_(t) is —C(O)—R_(tt), and binds a group     —Y′—ONO₂     can be obtained as follows: -   101a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—C(O)—:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 101., A is a radical of (IIa),     (IIc) or (IIt) wherein R₂, d, d′, R_(t) are as defined in 101.,     R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—C(O)—; R_(i) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   101a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     R_(ii)—OC(O)—;     by reacting a compound of formula (VIIIL)

wherein Y and Y′ are as above defined; A_(13a) is a radical of formula (IIa), (IIc) wherein R₁ is the —Fmoc protective group;

-   R₂ is —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(a) of formula (IIa)     and R_(c) of formula (IIc) are R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i)     is R_(ii)—C(O)— and binds a group —Y′—ONO₂ known procedure to remove     the —Fmoc protective groups; -   101b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) with a compound of formula     (IIIe)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; —R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂; R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p as above defined and R_(h) is —H; in formula (IIt) d and d′ are as above defined, and R_(t) is —H; using the same procedure described in 1b′).

-   101b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H:     Compound (VIIIL) are prepared by reacting a compound of formula     (VIIIm) with a compound of formula (IIIe)

wherein Y and Y′ are as above defined, and A₁₃ is a radical of formula (IIa), (IIc) wherein R₁ is the Fmoc protective group, R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is —H using the same procedure described in 1b′).

-   101c) R_(a)=R_(c) are selected from R_(ha)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(ha) is —Fmoc:     by deprotecting the Fmoc group of a compound of formula (VIIIn)

wherein Y is as above defined and A₁₄ as a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(ha)NH(CH₂)_(p)— wherein p as above defined, and R_(ha) is the Fmoc protective group; d and d′ are as above defined, and R_(t) is equal to R_(ta) and is the Fmoc protective group

-   101′c) R_(a)=R_(c) selected from R_(ia)NH(═NH)NH—(CH₂)₃—,     R_(ia)=—Pbf     Compound (VIIIm) are prepared by deprotecting the —Pbf group of a     compound of formula (VIIIo)

wherein Y is as above defined, and A_(15a) is a radical of formula (IIa), (IIc) wherein R₁ is —Fmoc; R₂ is —C(O)OR_(2x) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(ia)NH(═NH)NH—(CH₂)₃— R_(ia) is —Pbf protective group;

-   101d) compound described in 101c) and 101c′) can be prepared by     reacting a compound of formula A₁₄ or A₁₅ with compound (IIIi) using     the same procedure described in 8b)     A₁₄+HO—Y—ONO₂→(VIIIn)  (IIIi)     A₁₅+HO—Y—ONO₂→(VIIIm)  (IIIi)     wherein Y is as above defined and: -   A₁₄ is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)OC(CH₃)₃; R₂ is —COOH; R_(a) and R_(c) are R_(ha)NH(CH₂)_(p)—     wherein p as above defined and by R_(ha) is Fmoc protective group; d     and d′ are as above defined, and R_(t) is R_(ta) and is the Fmoc     protective group. -   A₁₅ is a radical of formula (IIa), (IIc) wherein R₁ is —Fmoc; R₂ is     —COOH; R_(a) and R_(c) are selected from R_(ia)NH(═NH)NH—(CH₂)₃—,     wherein R_(ia) is —Pbf.     Compounds A₁₄ and A₁₅ are commercially available. -   102. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′ and m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H, R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)—, and binds a group —Y′—ONO₂ -   in formula (IIt) R₁ is —H, and R₂ is —C(O)OR_(2x) and binds a group     —Y—ONO₂; d is 2 d′ is 1, R_(t) is —C(O)O—R_(tt), and binds a group     —Y′—ONO₂     can be obtained as follows: -   102a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—OC(O)—:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 102., A is a radical of (IIa),     (IIc) or (IIt) wherein R₂, d, d′, R_(t) are as defined in -   102., R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p     is an integer from 0 to 4, R_(h) is R_(hh)—OC(O)—; R₁ is     —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   102a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     R_(ii)—OC(O)—;     by reacting a compound of formula (VIIIp)

wherein Y and Y′ are as above defined; A₁₆ is a radical of formula (IIa), (IIc) wherein R₁ is the —Fmoc protective group;

-   R₂ is —C(O)OR_(2x) and binds a group —Y′—ONO₂; R_(a) of formula     (IIa) and R_(c) of formula (IIc) are R_(i)NH(═NH)NH—(CH₂)₃— wherein     R_(i) is R_(ii)—OC(O)— and binds a group —Y′—ONO₂ by known procedure     to remove the —Fmoc protective groups; -   102b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is —H:     by reacting a compound of formula (I) with a compound of formula     (IIIf)

wherein Y and Y′ are as above defined and A is as above defined in 101b), using the same procedure described in 3b).

-   102b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H:     by reacting a compound of formula (VIIIm) already described in     101b′) and obtained as described in 101c′) with a compound of     formula (IIIf)

wherein Y and Y′ are as above defined and A_(13′) is as defined in 101b′) using the same procedure described in 3b).

-   103. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′ and m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H, R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)—, and binds a group —Y′—ONO₂ -   in formula (IIt) R₁ is —H, and R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂; d is 2 d′ is 1, R_(t)     is —C(O)—R_(tt), and binds a group —Y′—ONO₂     can be obtained as follows: -   103a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—C(O):     by reacting a compound of formula (I) wherein s, s′, a″, m, m′, m″,     Y, Y′, Y″ are as above defined in 103., A is a radical of (IIa),     (IIc) or (IIt) wherein R₂, d, d′, R_(t) are as defined in 103.,     R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—C(O)—; R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   103a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     R_(ii)—C(O)—;     by reacting a compound of formula (VIIIq)

wherein Y and Y′ are as above defined; A_(17a) is a radical of formula (IIa), (IIc) wherein R₁ is the —Fmoc protective group; R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂; R_(a) of formula (IIa) and R_(c) of formula (IIc) are R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is R_(ii)—C(O)— and binds a group —Y′—ONO₂ by known procedure to remove the —Fmoc protective groups;

-   103b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) with a compound of formula     (IIIe)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; —R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(h)NH(CH₂)_(p)— wherein p as above defined and R_(h) is —H; in formula (IIt) d and d′ are as above defined, and R_(t) is —H; using the same procedure described in 1b′).

-   103b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H:     by reacting a compound of formula (VIIIr) with a compound of formula     (IIIe)

wherein Y and Y′ are as above defined and A₁₇ is a radical of formula (IIa), (IIc) wherein R₁ is the Fmoc protective group, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is —H using the same procedure described in 1b′).

-   103c) R_(a)=R_(c) are selected from R_(ha)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(ha) is —Fmoc

Compound (I) described in 103b) can be prepared by deprotecting the Fmoc group of a compound of formula (VIIIs)

wherein Y is as above defined and A₁₈ is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; —R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(ha)NH(CH₂)_(p)— wherein p as above defined and R_(ha) is the Fmoc protective group; d and d′ are as above defined, and R_(t) is R_(ta) and is the Fmoc group.

-   103c′) R_(a)=R_(c) selected from R_(ia)NH(═NH)NH—(CH₂)₃—,     R_(ia)=—Pbf     Compound (VIIIr) described in 103b′) by deprotecting the —Pbf group     of a compound of formula (IIIt)

wherein Y is as above defined and A₁₉ is a radical of formula (IIa), (IIc) wherein R₁ is —Fmoc; —R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; R_(a) and R_(c) are R_(ia)NH(═NH)NH—(CH₂)₃— R_(ia) is the —Pbf protective group;

-   103d) compounds described in 103c) and 103c′) can be prepared by     reacting a compound of formula A₁₄ or A₁₅ described in 101d) with     compound (IIIo) using the same procedure described in 7b)     A₁₄+W₃NH—Y—ONO₂→(VIIIs)  (IIIo)     A₁₅+W₃NH—Y—ONO₂→(VIIIt)  (IIIo)     wherein Y is as above defined and W₃ is H or —CH₃. -   104. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′ and m″ are equal to 0;     Y and Y′ can be equal or different and are as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H, R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is as integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)—, and binds a group —Y′—ONO₂; -   in formula (IIt) R₁ is —H; and R₂ is —C(O)NHR_(2xx) or     —C(O)N(CH₃)R_(2xx) and binds the group —Y—ONO₂; d is 2 d′ is 1,     R_(t) is —C(O)O—R_(tt), and binds a group —Y′—ONO₂     can be obtained as follows: -   104a) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is R_(hh)—O—C(O)—:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 104., A is a radical of (IIa),     (IIc) or (IIt) wherein R₂, d, d′, R_(t) are as defined in 104.,     R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—O—C(O)—; R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   104a′) R_(a)=R_(c) are selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i)     is R_(ii)—OC(O)—;     by reacting a compound of formula (VIIIu)

wherein Y and Y′ are as above defined and A₂₀ is a radical of formula (IIa), (IIc) wherein R₁ is the —Fmoc protective group;

-   R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group     —Y—ONO₂; R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is R_(ii)—OC(O)— and binds a     group —Y′—ONO₂ by known procedure to remove the —Fmoc protective     groups; -   104b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) with a compound of formula     (IIIf)

wherein Y and Y′ are as above defined and A is as defined in 103b), using the same procedure described in 3b).

-   104b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H:     Compound (VIIIu) can be prepared by reacting a compound of formula     (VIIIr) with a compound of formula (IIIf)

wherein Y and Y′ are as above defined and A₁₇ is as defined in 103b′) using the same procedure described in 3b).

-   105. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′ and m″ are equal to 0; -   Y and Y′ are as above defined; -   B is:

-   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H, —R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)—, and bind a group —Y′—ONO₂ -   in formula (IIt) R₁ is —H, and R₂ is —C(O)OR_(2x) and binds a group     —B—Y—ONO₂, d is 2 d′ is 1, R_(t) is —C(O)—R_(tt) and binds a group     —Y′—ONO₂;     can be obtained as follows: -   105a) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is R_(hh)—C(O)—:     by reacting a compound of formula (I) wherein s, s′, a″, m, m′, m″,     B, Y, Y′, Y″ are an above defined in 105., A is a radical of (IIa),     (IIc) or (IIt) wherein R₂, d, d′, R_(t) are as defined in 105.,     R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —R_(hh)—C(O)—; R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   105a′) R_(a)=R_(c) are selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i)     is R_(ii)—OC(O)—; by reacting a compound of formula (VIIIv)

wherein B, Y and Y′ are as above defined and A_(21a) is a radical of formula (IIa), (IIc) wherein R₁ is the —Fmoc protective group;

-   R₂ is —C(O)OR_(2x) and binds the group —B—Y—ONO₂; R_(a) of formula     (IIa) and R_(c) of formula (IIc) are R_(i)NH(═NH)NH—(CH₂)₃ wherein     R_(i) is R_(ii)—C(O)— and binds a group —Y′—ONO₂ by known procedure     to remove the —Fmoc protective groups; -   105b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) with a compound of formula     (IIIe)

wherein Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; —R₂ is —C(O)OR_(2x) and binds the group —B—Y—ONO₂; R_(a) and R_(c) are R_(h)NH(CH₂)_(p)— wherein p as above defined and R_(h) is —H; in formula (IIt) d and d′ are as above defined, and R_(t) is —H; using the same procedure described in 1b′);

-   105b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H:     Compound of formula (VIIIv) can be prepared by reacting a compound     of formula (VIIIw) with a compound of formula (IIIe)

wherein Y and Y′ are as above defined and A₂₁ is a radical of formula (IIa), (IIc) wherein R₁ is the Fmoc protective group, R₂ is —C(O)OR_(2x) and binds the group —B—Y—ONO₂; R_(a) and R_(c) are R_(i)NH(═NH)NH—(CH₂)₃— wherein R₁ is —H using the same procedure described in 1b′).

-   105c) R_(a)=R_(c) are selected from R_(ha)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(ha) is —Fmoc     Compound (I) described in 105b) by deprotecting the Fmoc group of a     compound of formula (VIIIx)

wherein Y and B are as above defined and A₂₂ is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is —C(O)OR_(2x) and binds the group —B—Y—ONO₂; R_(a) and R_(c) are R_(ha)NH(CH₂)_(p)— wherein p as above defined and R_(ha) is the Fmoc protective group; d and d′ are as above defined, and R_(t) is R_(ta) and is the Fmoc protecting group.

-   105c′) R_(a)=R_(c) selected from R_(ia)NH(═NH)NH—(CH₂)₃—,     R_(ia)=—Pbf     Compound described in 105b′) are prepared by deprotecting the —Pbf     group of a compound of formula (VIIIy)

wherein Y is as above defined and A₂₃ is a radical of formula (IIa), (IIc) wherein R₁ is —Fmoc; R₂ is —C(O)OR_(2x) and binds the group —B—Y—ONO₂; R_(a) and R_(c) R_(ia)NH(═NH)NH—(CH₂)₃— R_(ia) is the —Pbf protective group;

-   105d) compounds (VIIIx) and (VIIIy) are prepared by reacting     respectively a compound of formula A₁₄ or A₁₅ described in 101d)     with compound (IIIg) or (IIIn) depending on the meaning of B, and     applying the same procedure described in 4b) or 6b):     A₁₄ or A₁₅+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     A₁₄ or A₁₅+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     wherein Hal, W₁ and Y are as above. -   106. The compounds of general formula (I) wherein: -   s s′ and m are equal to 1; -   s″, m′ and m″ are equal to 0; -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is —H, -   R₂ is —C(O)OR_(2x) and binds a group —B—Y—ONO₂; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)—, and bind a group —Y′—ONO₂ -   in formula (IIt) R₁ is —H, and R₂ is —C(O)OR_(2x) and binds a group     —B—Y—ONO₂, d is 2 d′ is 1, R_(t) is —C(O)O—R_(tt) and binds a group     —Y′—ONO₂;     can be obtained as follows: -   106a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is R_(hh)—OC(O)—:     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     B, Y, Y′, Y″ are as above defined in 106., A is a radical of (IIa),     (IIc) or (IIt) wherein R₂, d, d′, R_(t) are as defined in 106.,     R_(a) and R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —R_(hh)—OC(O)—; R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   106a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     R_(ii)—OC(O)—;     by reacting a compound of formula (VIIIz)

wherein B, Y and Y′ are as above defined and A₂₄ is a radical of formula (IIa), (IIc) wherein R₁ is the —Fmoc protective group; R₂ is —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(a) of formula (IIa) and R_(c) of formula (IIc) are R_(i)NH(═NH)NH—(CH₂)₃— wherein R_(i) is R_(ii)—OC(O)— and binds a group —Y′—ONO₂ by known procedure to remove the —Fmoc protective groups;

-   106b) R_(a)=R_(c) are selected from R_(h)NH(CH₂)_(p)— wherein p is     an integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) obtained as described in 105c)     with a compound of formula (IIIf)

wherein Act, B, Y and Y′ are as above defined and A is as defined in 105b), using the same procedure described in 3b).

-   106b′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H:     by reacting a compound of formula (VIIIw) obtained as described in     105c′) with a compound of formula (IIIf)

wherein B, Y and Y′ are as above defined and A₂₁ is as defined in 105b′), using the same procedure described in 3b).

-   107. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is —COOH -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are —H;     an formula (IIt) d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   107a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 107., A is a radical of (IIa),     (IIc) or (IIt) wherein R₁, R₂, d, d′, are as defined in 107., R_(a)     of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   107a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H;     reacting a compound of formula (VIIIaa)     A₂₅-Y—ONO₂  (VIIIaa)     wherein Y is as above defined and A₂₅ is a radical of formula (IIa),     (IIc) wherein R₁, R₂ are as defined in 107., R_(a) of formula (IIa)     and R_(c) of formula (IIc) are selected from     R_(ia)NH(═NH)NH—(CH₂)₃—, wherein R_(ia) is the —Pbf protective group     as already defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   107b) compounds described in 107a) and 107a′) can be prepared by     reacting a compound of formula A or a compound of formula A₂₆ with a     compound of formula (IIIe)     A+Act(O)C—Y—ONO₂→(I)  (IIIe)     A₂₆+Act(O)C—Y—ONO₂→(VIIIaa)  (IIIe)     wherein Act and Y are as above defined and: -   A is a compound of formula (IIa), (IIc) or (IIt) wherein R₁ is —H,     R₂ is —COOH; R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; in formula (IIt) d and d′ are as defined on 107.,     R_(t) is —C(O)OC(CH₃)₃; -   A₂₆ is a compound of formula (IIa) or (IIc) wherein R₁ is —H, R₂ is     —COOH; R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(ia)NH(═NH)NH—(CH₂)₃—, wherein R_(ia) is the —Pbf protective group     as already defined;     using the same procedure described in 1b′),     Compounds A and A₂₆ are commercially available. -   108. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and binds a group —Y—ONO₂; R₂ is —COOH -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer front 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are —H; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   108a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 108., A is a radical of (IIa),     (IIc) or (IIt) wherein R₁, R₂, d, d′, are as defined in 108., R_(a)     of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   108a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H;     reacting a compound of formula (VIIIab)     A₂₇-Y—ONO₂  (VIIIab)     wherein Y is as above defined and A₂₇ is a radical of (IIa), (IIc)     wherein R₁, R₂, are as defined in 108., R_(a) of formula (IIa) and     R_(c) of formula (IIc) are selected from R_(ia)NH(═NH)NH—(CH₂)₃—,     wherein R_(ia) is the —Pbf protective group as already defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature.     108b) compounds described in 108a) and 108a′) can be prepared by     reacting a compound of formula A or a compound of formula A₂₆ both     already defined in 107b) with a compound of formula (IIIf)     A+Act(O)C—O—Y—ONO₂→(I)  (IIIf)     A₂₆+Act(O)C—O—Y—ONO₂→(VIIIab)  (IIIf)     wherein Act and Y are as above defined, using the same procedure     described, in 3b). -   109. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H; R₂ is     —COOH; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—C(O)— or     R_(ii)—C(O)—, and bind a group —Y—ONO₂; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —C(O)—R_(tt), and binds a     group —Y—ONO₂;     can be obtained as follows: -   109a) by reacting a compound of formula (I) wherein s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 109., A is a radical of     (IIa), (IIc) or (IIt) wherein R₂, R_(a), R_(c), d, d′ and R_(t) are     as defined in 109., R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   109b) by reacting a compound of formula A with a compound of formula     (IIIe)     A+Act(O)C—Y—ONO₂  (IIIe)     wherein Act and Y are as above defined and A is a radical of (IIa),     (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is —COOH; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are —H; -   in formula (IIt) d and d′ are as defined in 109., R_(t) is —H;     using the same procedure described in 1b′).     Compounds A are commercially available. -   110. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H, R₂ is     —COOH; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)—, and bind a group —Y—ONO₂; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —C(O)O—R_(tt), and it     binds a group —Y—ONO₂;     can be obtained as follows: -   110a) by reacting a compound of formula (I) wherein s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 110., A is a radical of     (IIa), (IIc) or (IIt) wherein R₂, R_(a), R_(c), d, d′ and R_(t) are     as defined in 110., R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   110b) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act(O)C—O—Y—ONO₂  (IIIf)     wherein Act and Y are as above defined and A is as defined in 109b),     using the same procedure described in 3b). -   111. The compounds of general formula (I) wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are equal to 0; -   Y and Y′ are equal or different and are as above defined; -   B is:

-   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y—ONO₂; R₁ is selected from R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—,     R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y′—ONO₂; R_(c) is selected from R_(bx)—C(O)—S—CH₂—, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(c) binds a group —Y—ONO₂;     iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)R_(3x) and R₃ binds a group     —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(s) binds a group B—Y′—ONO₂; -   v) (IIn), wherein R₁ is —H, R₂ is —C(O)OR_(2x), R₂ binds a group     B—Y′—ONO₂; a is 1, b is 0 or 1; R_(x) is R_(xx)—C(O)— and R_(x)     binds a group —Y—ONO₂;     can be prepared as follows: -   111a) by reacting a compound of formula (I) wherein B, s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 111., A is a radical, of     formula (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a),     R_(c), R_(g) and R_(x), are as defined in 111.; R₁ is —C(O)OC(CH₃)₃,     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   111b) by reacting a compound of formula (I) obtained in 36b) with a     compound of formula (IIIg) or (IIIn) depending on the meaning of B

wherein Y and Y′, Hal, W₁ are as above defined and in formula (I) A is selected among:

-   i) (IIa) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R_(a) is selected     from R_(bx)—C(O)—S—CH₂—, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, R_(c) is     selected from R_(bx)—C(O)—S—CH₂, or R_(x)O—CH₂—, R_(x)O—CH(CH₃)—,     (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—C(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —C(O)OC(CH₃)₃, R₃ is —OC(O)R_(3x) and R₃     binds a group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     —OH, -   v) (IIu) wherein R₁ is —C(O)OC(CH₃)₃, R₂ is —COOH, a is 1, b is 0 or     1; and R_(x) is R_(xx)—C(O)— and R_(x) binds a group —Y′—ONO₂;     following the same procedures described in 4b) or 6b). -   112. The compounds of general formula (I) wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   B is

-   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y′—ONO₂; and R_(a) is selected from R_(bx)—OC(O)—S—CH₂, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(a) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y′—ONO₂; R_(c) is selected from R_(bx)—OC(O)—S—CH₂, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)—OC(O)— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)O—R_(3x) and R₃ binds a     group —Y—ONO₂; R_(s) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     R_(gx)—O—, and R_(s) binds a group B—Y′—ONO₂; -   v) wherein R₁ is —H, R₂ is —C(O)OR_(2x), R₂ binds a group     —B—Y′—ONO₂; a is 1; b is 0 or 1; R_(x) is R_(xx)—OC(O)— and R_(x)     binds a group —Y—ONO₂;     can be prepared as follows: -   112a) by reacting a compound of formula (I) wherein B, s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 112., A is a radical of     formula (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a),     R_(c), R_(g) and R_(x), are as defined in 112.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   112b) by reacting a compound of formula (I) obtained in 37b) with a     compound of formula (IIIg) or (IIIn) depending on the meaning of B

wherein Y and Y′, Hal, W₁ are as above defined and in formula (I) A is as above defined in 111b); following the same procedures described in 4b) or 6b).

-   113. The compounds of general formula (I) wherein: -   s, s′ and m′ are equal to 1; -   s″, m, m″, are 0 -   Y and Y′ are equal or different and are as above defined; -   B is:

-   A is selected among: -   i) (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y′—ONO₂; and R_(a) is selected from R_(bx)—NH(O)C—S—CH₂, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH(O)C— and R_(c) binds a group —Y—ONO₂; -   ii) (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     B—Y′—ONO₂; R_(c) is selected from R_(bx)—NH(O)C—S—CH₂, or     R_(x)O—CH₂—, R_(x)O—CH(CH₃)—, (R_(x)O)-p-C₆H₄—CH₂—,     4-(R_(x)O)-3,5-diiodobenzyl-4-(R_(x)O)-3-nitrobenzyl- wherein R_(x)     is R_(xx)NH(O)C— and R_(c) binds a group —Y—ONO₂; -   iii) (IIs) wherein R₁ is —H, R₃ is —OC(O)—NH—R_(3x) and R₃ binds a     group —Y—ONO₂; R₃ is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(g) binds a group B—Y′—ONO₂; -   v) (IIu) wherein R₁ is —H, R₂ is —C(O)OR_(2x), and R₂ binds a group     B—Y′—ONO₂; a is 1; b is 0 or 1; R_(x) is R_(xx)NHC(O)— and R_(x)     binds a group —Y—ONO₂;     can be prepared as follows: -   113a) by reacting a compound of formula (I) wherein B, s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 113., A is a radical of     formula (IIa), (IIc), (IIs) or (IIu) wherein; R₂, R₃, a, b, R_(a),     R_(c), R_(g) and R_(x), are as defined in 113.; R₁ is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   113b) by reacting a compound of formula (I) obtained in 38b) with a     compound of formula (IIIg) or (IIIn) depending on the meaning of B

wherein Y and Y′, Hal, W₁ are as above defined and in formula (I)

-   A is as above defined in 111b);     following the same procedures described in 4b) or 6b). -   114. The compounds of general formula (I) wherein: -   s is equal to 1; -   m, m′, m″, s′ and s″ are 0 -   Y is as above defined; -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)—R_(1x) and it binds the group —Y—ONO₂, R₂     is equal to the group R₄

-   in formula (IIn) R_(n) is —C(O)—R_(nx), or is —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)R_(hh) and it binds the group —Y—ONO₂ -   R_(a) of formula (IIa) is selected in group a) -   R_(c) of formula (IIc) is selected in group a′) -   in formula (IIt) d is an integer from 3 to 5, d′ is 0; -   can be prepared as follows -   114a) by reacting a compound of formula A with a compound of formula     (IIIa) or a compound of formula (IIIe)     A+HOOC—Y—ONO₂  (IIIa)     A+Act-CO—Y—ONO₂  (IIIe)     wherein Y is as above defined and A is selected from (IIa)-(IIm),     (IIo)-(IIr), (IIt)-(IIu) and (IIn) wherein R₁ is —H and R₂ is as     above defined in 114.; -   in formula (IIn) R_(n) is H, or is —(CH₂)₂—NH—R_(h) wherein R_(h) is     H; -   R_(a) of formula (IIa) is selected in group a); -   R_(c) of formula (IIc) is selected in group a′); -   in formula (IIt) d and d′ are as above defined;     following the same procedure described in 1b) or 1b′). -   114b) compounds A as above defined can be prepared by reacting     commercially available compounds of formula A₂ described in 1c)     wherein A₂ is a radical of formula (IIa)-(IIm), (IIo)-(IIr),     (IIt)-(IIu) and (IIn) wherein R₂—COOH or R_(2a) wherein R_(2a) is     the group —COAct as already described in 8., R₁ is —C(O)OC(CH₃)₃,     R_(n) is —C(O)OC(CH₃)₃ or is —(CH₂)₂—NH—C(O)OC(CH₃)₃, R_(a), R_(c),     d and d′ are as defined in 114., with compounds (IIIx) or (IIIy):

-   In case of (IIIx): in the presence of a inorganic or organic base in     an aprotic polar or in an aprotic non-polar solvent such as DMF, THF     or CH₂Cl₂ at temperatures range between 0° to 100° C.; -   In case of (IIIy) following the same procedure described in 8b) for     R₂ equal to —COOH or equal to R_(2a) wherein R_(2a) is the group     —COAct. Compound (IIIx) is commercially available. Compound (IIIy)     can be obtained from (IIIx) by first reacting with formic acid and     TEA in acetonitrile and then hydrolyzing the formyl ester with     hydrochloric acid in methanol/water at room temperature, as     described for analogous compounds by Alexander in J. Med. Chem.     1996, 39, 480-486. -   115. The compounds of general formula (I) wherein: -   s is equal to 1; -   m, m′, m″, s′ and s″ are 0 -   Y is as above defined, -   A is a radical of formula (IIa)-(IIm), (IIo)-(IIr), (IIt)-(IIu) and     (IIn) wherein R₁ is —C(O)O—R_(1x) and it binds the group —Y—ONO₂, R₂     is equal to R₄, wherein R₄ is as defined in 114.; -   in formula (IIn) R_(n) is —C(O)O—R_(nx) or —(CH₂)₂—NH—R_(h)     wherein R_(h) is —C(O)O—R_(hh), and it binds the group —Y—ONO₂ -   R_(a) of formula (IIa) is selected in group a) -   R_(c) of formula (IIc) is selected in group a′) -   in formula (IIt) d is an integer from 3 to 5, d′ is 0;     can be prepared as follows -   115a) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act-(O)C—O—Y—ONO₂  (IIIf)     wherein A is as above reported in 114a), Act and Y are as already     defined, following the same procedure described in 3b). -   116. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —Y—ONO₂; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is equal to R_(gg)     and is equal to:

-   (IIc) wherein R₁ is —H, R₂ is equal to —C(O)OR_(2x) and R₂ binds a     group —Y—ONO₂; R_(c) is selected from R_(g)C(O)CH₂—NH—,     R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is     equal to R_(gg) and is as above defined can be prepared as follows: -   116a) by reacting a compound of formula (VIIIa)     A_(28a)-Y—ONO₂  (IXa)     wherein Y is as above defined and A_(28a) is a radical of formula     (IIa), (IIc), wherein R₂ is as above defined in 116.; R₁ is R_(1a)     and is the Fmoc group; R_(a) and R_(c) are R_(gg)C(O)CH₂—NH—,     R_(gg)C(O)CH₂, R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg)     is as above defined by known procedure to remove the —Fmoc     protective groups; -   116b) by reacting a compound of formula A₂₈ with a compound of     formula (IIIi)     A₂₈+HO—Y—ONO₂  (IIIi)     wherein Y is as above defined and R₂₈ is a compound of formula (IIa)     or (IIc) wherein R₁ is R_(1a) and is the Fmoc group; R₂ is —COOH,     R_(a) and R_(c) are selected from R_(gg)C(O)CH₂—NH—, R_(gg)C(O)CH₂,     R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg) is as above     defined in 116.;     following the same procedure described in 8b). -   116c) by reacting a compound A₂₉     A₂₉→A₂₈     wherein R₁ is R_(1a) is the Fmoc group; R₂ is —C(O)OC(CH₃)₃; R_(a)     and R_(c) are selected from R_(gg)C(O)CH₂—NH—, R_(gg)C(O)CH₂,     R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg) is as above     defined in 116 with anhydrous or aqueous organic or inorganic acid,     as well known in the literature to remove the t-butyl ester. -   116d) by reacting a compound A₃₀     A₃₀→A₂₉     wherein R₁ is R_(1a) and is the Fmoc group; R₂ is —C(O)OC(CH₃)₃;     R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —OH with     compounds (IIIx) or (IIIy) as described in 114b). Compounds A₃₀ are     commercially available. -   117. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   R is a radical of formula -   (IIa) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and R₂ binds a group —Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gg) and is as defined in 116.; or -   (IIc) wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx)     and R₂ binds a group —Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gg) and is as defined in 116.; can be prepared     as follows: -   117a) by reacting a compound of formula (IXb)     A₃₁-Y—ONO₂  (IXb)     wherein Y is as above defined and A₃₁ is a radical of formula (IIa),     (IIc), wherein R₂ is as above defined in 117.; R₁ is R_(1a) and is     the Fmoc group; R_(a) and R_(c) are R_(gg)C(O)CH₂—NH—,     R_(gg)C(O)CH₂, R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg)     is as above defined by known procedure to remove the —Fmoc     protective groups; -   117b) by reacting a compound of formula A₂₈ with a compound of     formula (IIIo)     A₂₈+W₃NH—Y—ONO₂→(IXb)  (IIIo)     wherein Y is as above defined, W₃ is as above defined and A₂₈ is as     defined in 116b),     following the same procedure described in 7b). -   118. The compounds, of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″, are 0 -   Y is as above defined; -   B is:

-   A is a radical selected among: -   (IIa) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —B—Y—ONO₂; R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gg) and is     as defined in 116., -   (IIc) wherein R₁ is —H, R₂ is —C(O)OR_(2x) and R₂ binds a group     —B—Y—ONO₂; R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gg) and is     as defined in 116.; can be prepared as follows: -   118a) by reacting a compound of formula (VIIIc)     A_(28a)-B—Y—ONO₂  (IXc)     wherein B and Y are as above defined and A_(28a) is as defined in     116a) a radical of formula (IIa), (IIc), wherein R₂ is as above     defined in 118.; R₁ is R_(1a) the Fmoc group; R_(a) and R_(c) are     R_(gg)C(O)CH₂—NH—, R_(gg)C(O)CH₂, R_(gg)C(O)(CH₂)₂—,     R_(gg)C(O)(CH₂)₄—, wherein R_(gg) is as above defined by known     procedure to remove the —Fmoc protective groups; -   118b) compound (IXc) are prepared by reacting a compound of formula     A₂₈ with a compound of formula (IIIg) or (IIIn) depending on the     meaning of B     A₂₈+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     A₂₈+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     wherein Y, Hal, W₁ are as above defined and A₂₈ is as defined in     116b),     following the same procedures described in 4b) or 6b). -   119. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is equal to R₄ and is as defined in 114.;     R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(g) binds a group —Y—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is equal to R₄ and is as defined in 114.;     R_(a) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and     R_(g) binds a group —Y—ONO₂, can be prepared as follows: -   119a) by reacting a compound of formula (Xa)     A₃₂-Y—ONO₂  (Xa)     wherein Y is as above defined and A₃₂ is a radical of formula (IIa),     (IIc), wherein R_(a) and R_(c) are as above defined in 119.; R₁ is     —R_(1a) and is the Fmoc group; R₂ is R₄ and is as defined in 114.;     following procedure well known in the literature to remove the Fmoc     group. -   119b) by reacting a compound of formula A₃₃ with a compound of     formula (IIIi)     A₃₃+HO—Y—ONO₂→(Xa)  (IIIi)     wherein Y is as above defined and A₃₃ is a radical of formula (IIa),     (IIc) wherein R₁ is —R_(1a) and is the Fmoc group; R₂ is R₄ and is     as defined in 114.; R_(a) and R_(c) are selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(c) is —OH;     following the same procedure described in 8b). -   119c) by reacting a compound A₃₄     A₃₄→A₃₃     wherein R₁ is R_(1a) and is the Fmoc group; R₂ is R₄; R_(a) and     R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —C(O)OC(CH₃)₃     with anhydrous or aqueous organic or inorganic acid as well known in     the literature to remove the t-butyl ester. -   119d) by reacting a compound A₃₅     A₃₅→A₃₄     wherein R₁ is R_(1a) and is the Fmoc group; R₂ is —COOH; R_(a) and     R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is —C(O)OC(CH₃)₃     with compounds (IIIx) or (IIIy) as described in 114b). Compounds A₃₅     are commercially available. -   120. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″, are 0 -   Y is as above defined; -   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is R₄ and is as defined in 114.; R_(a) is     selected R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)—     and R_(g) binds a group —Y—ONO₂; -   (IIc) wherein R₁ is —H, R₂ is R₄ and is as defined in 114.; R_(c) is     selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)—     and R_(g) binds a group —Y—ONO₂;     can be prepared as follows: -   120a) by reacting a compound of formula (Xb)     A₃₆-Y—ONO₂  (Xb)     wherein Y is as above defined and A₃₆ is a radical of formula (IIa),     (IIc), wherein R_(a) and R_(c) are as above defined in 120.; R₁ is     R_(1a) and is the Fmoc group; R₂ is R₄ and is as defined in 114.;     following procedure well known in the literature to remove the Fmoc     group. -   120b) by reacting a compound of formula A₃₃ with a compound of     formula (IIIo):     A₃₃+W₃NH—Y—ONO₂→(Xb)  (IIIo)     wherein Y and W₃ are as above defined and A₃₃ is as defined in 119b)     following the same procedure described in 7b). -   121. The compounds of general formula (I) wherein: -   s and m are equal to 1; -   s′, s″, m′, m″, are 0 -   Y is as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —H, R₂ is R₄ and is as defined in 114.; R_(a) is     selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O— and R_(g) binds a group     —B—Y—ONO₂; -   (IIc) wherein R₁ is —H, and R₂ is R₄ as defined in 114.; R_(c) is     selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and R_(g) binds a     group —B—Y—ONO₂;     can be prepared as follows: -   121a) by reacting a compound of formula (Xc)     A₃₇-B—Y ONO₂  (Xc)     wherein B and Y are as above defined and A₃₇ is a radical of formula     (IIa), (IIc), wherein R_(a) and R_(c) are as above defined in 121.;     R₁ is R_(1a) and is the Fmoc group; R₂ is R₄ and is as defined in     114.,     following procedure well known in the literature to remove the Fmoc     group. -   121b) compounds (Xc) are prepared by reacting a compound of formula     A₃₃ with a compound of formula of formula (IIIg) or (IIIn) depending     on the meaning of B     A₃₃+Hal-W₁—OC(O)O—Y—ONO₂  (IIIg)     A₃₃+Hal-W₁—OC(O)—Y—ONO₂  (IIIn)     wherein Y, Hal, W₁ are as above defined and A₃ is as defined in     119b),     following the same procedures described in 4b) or 6b). -   122. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116., -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116.; can be     prepared as follows: -   122a) by reacting a compound of formula (I) prepared as described     in 116. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(a) and R_(c) are selected from R_(gg)C(O)CH₂—NH—, R_(gg)C(O)CH₂, R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg) is as above defined; following the same procedures described in 1b′).

-   123. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116., -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116.; can be     prepared as follows: -   123a) by reacting a compound of formula (I) prepared as described     in 116. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is as defined in 122a);

-   following the same procedures described in 3b). -   124. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂;     R_(a) is selected R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is equal to R_(gg) and is as defined     in 116., -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂;     R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is equal to R_(gg)     and is as defined in 116.; can be prepared as follows: -   124a) by reacting a compound of formula (I) prepared as described     in 117. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —C(O)NHR_(2xx) or —C(O)NCH₃R_(2xx) binds a group —Y—ONO₂; R_(a) and R_(c) are selected from R_(gg)C(O)CH₂—NH—, R_(gg)C(O)CH₂, R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg) is as above defined; following the same procedures described in 1b′).

-   125. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R_(a) is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂     is —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂;     R_(a) is selected R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—,     R_(g)C(O)(CH₂)₄—, wherein R_(g) is equal to R_(gg) and is as defined     in 116., -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)NHR_(2xx) or —C(O)N(CH₃)R_(2xx) and binds a group —Y—ONO₂;     R_(c) is selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂,     R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is equal to R_(gg)     and is as defined in 116.; can be prepared as follows: -   125a) by reacting a compound of formula (I) prepared as described     in 117. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is as above defined in 124a), following the same procedures described in 3b).

-   126. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116.; -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116.;     can be prepared as follows. -   126a) by reacting a compound of formula (I) prepared as described     in 118. with a compound of formula (IIIe):

wherein Act, B, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is —C(O)OR_(2x) and binds a group B—Y—ONO₂; R_(a) and R_(c) are selected from R_(gg)C(O)CH₂—NH—, R_(gg)C(O)CH₂, R_(gg)C(O)(CH₂)₂—, R_(gg)C(O)(CH₂)₄—, wherein R_(gg) is as above defined; following the same procedures described in 1b′).

-   127. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116.; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     —C(O)OR_(2x) and binds a group —B—Y—ONO₂; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is equal to R_(gg) and is as defined in 116.; can be     prepared as follows: -   127a) by reacting a compound of formula (I) prepared as described     in 118. with a compound of formula (IIIf):

wherein Act, B, Y and Y′ are as above defined and A is as defined in 126a), following the same procedures described in 3b).

-   128. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂; R₂     is equal to R₄ and is as defined in 114.; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and binds a group —Y—ONO₂ -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     equal to R₄ and is as defined in 114.; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O— and binds a group —Y′—ONO₂;     can be prepared as follows: -   128a) by reacting a compound of formula (I) prepared as described     in 119. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is equal to R₄; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)—O—, and binds a group —Y′—ONO₂ following the same procedures described in 1b′).

-   129. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and it binds a group —Y′—ONO₂; R₂     is equal to R₄ and is as defined in 114.; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and binds a group —Y—ONO₂; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     equal to R₄ and is as defined in 114.; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)—O—, and binds a group —Y—ONO₂;     can be prepared as follows: -   129a) by reacting a compound of formula (I) prepared as described     in 119. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is equal to R₄; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O— and binds a group —Y—ONO₂, following the same procedures described in 3b).

-   130. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂; R₂     is equal to R₄ and is as defined in 114.; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— binds R_(a) binds a     group —Y—ONO₂ -   (IIc) wherein R₁ is —C(O)—R_(1x) and it binds a group —Y′—ONO₂; R₂     is equal to R₄ and is as defined in 114.; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and R_(c) binds a     group —Y—ONO₂;     can be prepared as follows: -   130a) be reacting a compound of formula (I) prepared as described     in 120. with a compound of formula (IIIe):

wherein Act, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is -equal to R₄; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and binds a group —Y—ONO₂ following the same procedures described in 1b′).

-   131. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     equal to R₄ and is as defined in 114.; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and binds a group     —Y—ONO₂ -   (IIc) wherein R₁ is —C(O)O—R_(1x) binds a group —Y′—ONO₂; R₂ is is     -equal to R₄ and is as defined in 114.; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gxx)—NH— or R_(gxx)—N(CH₃)— and binds a group     —Y—ONO₂;     can be prepared as follows: -   131a) by reacting a compound of formula (I) prepared as described     in 120. with a compound of formula (IIIf):

wherein Act, Y and Y′ are as above defined and A is as defined in 130a), following the same procedures described in 3b).

-   132. The compounds of general formula (I) wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     equal to R₄ and is as defined in 114.; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)O—, and binds a group —B—Y—ONO₂; -   (IIc) wherein R₁ is —C(O)—R_(1x) and binds a group —Y′—ONO₂; R₂ is     -equal to R₄ and is as defined in 114.; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)O—, and binds a group —B—Y—ONO₂;     can be prepared as follows: -   132a) by reacting a compound of formula (I) prepared as described     in 121. with a compound of formula (IIIe):

wherein Act, B, Y and Y′ are as above defined and A is a radical of formula (IIa), (IIc), wherein R₁ is —H, R₂ is equal R₄; R_(a) and R_(c) are selected from R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—, wherein R_(g) is R_(gx)O— and binds a group B—Y—ONO₂; following the same procedures described in 1b′).

-   133. The compounds of general formula (I), wherein: -   s, s′ and m are equal to 1; -   s″, m′, m″, are 0 -   Y and Y′ can be equal or different and are as above defined; -   B is:

-   A is selected among: -   (IIa) wherein R₁ is —C(O)O—R_(1x) and binds a group —Y′—ONO₂; R₂ is     equal to R₄ and is as defined in 114.; R_(a) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)O—, and binds a group —B—Y—ONO₂; -   (IIc) wherein R₁ is —C(O)O—R_(1x) and it binds a group —Y′—ONO₂; R₂     is equal to R₄ and is as defined in 114.; R_(c) is selected from     R_(g)C(O)CH₂—NH—, R_(g)C(O)CH₂, R_(g)C(O)(CH₂)₂—, R_(g)C(O)(CH₂)₄—,     wherein R_(g) is R_(gx)O— and R_(g) binds a group —B—Y—ONO₂;     can be prepared as follows: -   133a) by reacting a compound of formula (I) prepared as described     in 121. with a compound of formula (IIIf):

wherein Act, B, Y and Y′ are as above defined and A is as defined in 132a), following the same procedures described in 3b).

-   134. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″ are equal to 0; -   Y and Y′ are equal and are as above defined; -   A is selected from (IIa), (IIc) or (IIt) wherein R₁ is —C(O)—R_(1x)     and it binds a group —Y—ONO₂ or a group —Y′—ONO₂, R₂ is equal to R₄     and is as defined in 114.; R_(a) of formula (IIa) and R_(c) of     formula (IIc) are R_(h)NH(CH₂)_(p)— wherein p is an integer from 0     to 4, or R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are     R_(hh)—C(O)— or R_(ii)—C(O)— and R_(a) and R_(c) bind a group     —Y—ONO₂ or a group —Y′—ONO₂; -   in formula (IIt) R₁ is —C(O)—R_(1x) and it binds a group —Y—ONO₂ or     a group —Y′—ONO₂; R₂ is equal to R₄ and is as defined in 114.; d is     2 d′ is 1, R_(t) is —C(O)—R_(tt) and it binds a group —Y—ONO₂ or a     group —Y′—ONO₂;     can be prepared as follows: -   134a) by reacting a compound of formula A with a compound of formula     (IIIe)     A+Act-(O)C—Y—ONO₂  (IIIe)     wherein Act and Y are as above defined and A is a compound of     formula (IIa), (IIc) or (IIt) wherein R₁ is —H and R₂ is equal to     R₄; -   R₄ of formula (IIa) and R_(c) of formula (IIc) are R_(h)NH(CH₂)_(p)—     wherein p is an integer from 0 to 4, or R_(i)NH(═NH)NH—(CH₂)₃—, and     R_(h) and R_(i) are —H; -   in formula (IIt) R₁ is —H, R₂ is R₄; d is 2 d′ is 1, R_(t) is —H;     using a ratio A/(IIIe) 1:2 and applying the same procedure described     in 1b′). -   134b) by reacting a compound of formula A₃₈     A₃₈→A     wherein A₃₈ is a compound of formula (IIa), (IIc) or (IIt) wherein     R₁ is —C(O)OC(CH₃)₃ and R₂ is equal to R₄; -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4 and R_(h) is     —C(O)OC(CH₃)₃; or R_(ia)NH(═NH)NH—(CH₂)₃—, wherein R_(ia) is the     —Pbf group as already described; -   in formula (IIt) R₁ is —C(O)OC(CH₃)₃, is R₂ is R₄; d is 2 d′ is 1,     R_(t) is —C(O)OC(CH₃)₃;     with organic or inorganic acid as already described to hydrolize the     —BOC protecting groups; -   134c) by reacting commercially available compounds of formula A₃₉     with compounds (IIIx) or (IIIy) using the procedures described in     114b)     A₃₉+(IIIx)→A₃₈     A₃₉+(IIIy)→A₃₈     wherein A₃₉ is a radical of formula (IIa), (IIc) or (IIt) wherein R₁     is —C(O)OC(CH₃)₃ and R₂ is equal to —COOH or R_(2a) wherein R_(2a)     is as described in 8b); d is 2 d′ is 1, R_(t) is —C(O)OC(CH₃)₃;     R_(a) of formula (IIa) and R_(c) of formula (IIc) are: -   R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   or R_(ia)NH(═NH)NH—(CH₂)₃— wherein R_(ia) is as previously defined. -   135. The compounds of general formula (I) wherein: -   s and s′ are equal to 1; -   s″, m, m′, m″, are equal to 0; -   Y and Y′ are equal and are as above defined; -   A is a radical selected from (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and binds a group —Y—ONO₂ or a group —Y′—ONO₂; R₂ is     equal to R₄ and is as defined in 114., -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, and R_(h) and R_(i) are R_(hh)—OC(O)— or     R_(ii)—OC(O)— and R_(a) and R_(c) bind a group —Y—ONO₂ or a group     —Y′—ONO₂; -   in formula (IIt) R₁ is —C(O)O—R_(1x) and binds a group —Y—ONO₂ or a     group —Y′—ONO₂, R₂ is equal to R₄ and is as defined in 114.; d is 2     d′ is 1, R_(t) is —C(O)O—R_(tt) and binds a group —Y—ONO₂ or a group     —Y′—ONO₂;     can be prepared as follows: -   135a) by reacting a compound of formula A with a compound of formula     (IIIf)     A+Act-(O)C—O—Y—ONO₂  (IIIf)     wherein Act and Y are as above defined and A is as defined in 134a)     using a ratio A/(IIIf) 1:2 and applying the same procedure described     in 3b). -   136. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′, m″ are equal to 0; -   Y is as above defined; -   A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁ is     —C(O)—R_(1x) and binds a group —Y—ONO₂; R₂ is equal to R₄ and is as     defined in 114.; R_(a) of formula (IIa) and R_(c) of formula (IIc)     are R_(h)NH(CH₂)_(p)— wherein p is on integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are —H; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   136a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 136., A is a radical of (IIa),     (IIc) or (IIt) wherein R₁, R₂, d, d′, are as defined in 136., R_(a)     of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   136a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H;     reacting a compound of formula (Xd)     A₄₀-Y—ONO₂  (Xd)     wherein Y is as above defined and A₄₀ is a radical of formula (IIa),     (IIc) wherein R₁ and R₂ are as defined in 136., R_(a) of formula     (IIa) and R_(c) of formula (IIc) are selected from     R_(ia)NH(═NH)NH—(CH₂)₃—, wherein R_(ia) is the —Pbf protective group     as already defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   136b) compounds described in 136a) and 136a′) are respectively     obtained by reacting a compound of formula A₄₁ or a compound of     formula A₄₂ with a compound of formula (IIIe)     A₄₁+Act(O)C—Y′—ONO₂→(I)  (IIIe)     A₄₂+Act(O)C—Y′—ONO₂→(Xd)  (IIIe)     wherein Act and Y are as above defined and: -   A₄₁ is a compound of formula (IIa), (IIc) or (IIt) wherein R₁ is —H,     R₂ is equal to R₄; R_(a) of formula (IIa) and R_(c) of formula (IIc)     are R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; in formula (IIt) d and d′ are as defined, in 136., -   R_(t) is —C(O)OC(CH₃)₃; -   A₄₂ is a compound of formula (IIa) or (IIc) wherein R₁ is —H, R₂ is     equal to R₄; R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(ia)NH(═NH)NH—(CH₂)₃—, wherein R_(ia) is the —Pbf protective group     as already defined;     using the same procedure described 1b′). -   136c) compounds A₄₁ and A₄₂ are respectively obtained by reacting a     compound of formula A or a compound of formula A₂₆, both described     in 107b) with a compound of formula (IIIx) or (IIIy) as already     described in 114b). -   137. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is     —C(O)O—R_(1x) and binds a group —Y—ONO₂; R₂ is equal to R₄ and is as     defined in 114.; R_(a) of formula (IIa) and R_(c) of formula (IIc)     are R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃, wherein R_(h) and R_(i) are —H; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —H;     can be obtained as follows: -   137a) R_(a)=R_(c) selected from R_(h)NH(CH₂)_(p)— wherein p is an     integer from 0 to 4, R_(h) is —H     by reacting a compound of formula (I) wherein s, s′, s″, m, m′, m″,     Y, Y′, Y″ are as above defined in 137., A is a radical of (IIa),     (IIc) or (IIt) wherein R₁, R₂, d, d′, are as defined in 137., R_(a)     of formula (IIa) and R_(c) of formula (IIc) are selected from     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, R_(h) is     —C(O)OC(CH₃)₃; -   in formula (IIt) R_(t) is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   137a′) R_(a)=R_(c) selected from R_(i)NH(═NH)NH—(CH₂)₃—, R_(i) is     —H;     reacting a compound of formula (Xe)     A₄₃-Y—ONO₂  (Xe)     wherein Y is as above defined and A₄₃ is a radical of (IIa), (IIc)     wherein R₁ and R₂ are as defined in 137., R_(a) of formula (IIa) and     R_(c) of formula (IIc) are selected from R_(ia)NH(═NH)NH—(CH₂)₃—,     wherein R_(ia) is the Pbf protective group as already defined; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —Pbf protective groups following procedure well known in the     literature. -   137b) compounds described in 137a) and 137a′) are respectively     obtained by reacting a compound of formula A₄₁ or a compound of     formula A₄₂ both already defined in 136b) with a compound of formula     (IIIf)     A₄₁+Act(O)C—O—Y—ONO₂→(I)  (IIIf)     A₄₂+Act(O)C—O—Y—ONO₂→(Xe)  (IIIf)     wherein Act and Y are as above defined, using the same procedure     described in 3b). -   138. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H; R₂ is     equal to R₄ and is as defined in 114.; R_(a) of formula (IIa) and     R_(c) of formula (IIc) are R_(h)NH(CH₂)_(p)— wherein p is an integer     from 0 to 4, or R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are     R_(hh)—C(O)— or R_(ii)—C(O)—, and bind a group —Y—ONO₂; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —C(O)—R_(tt), and binds a     group —Y—ONO₂;     can be obtained as follows: -   138a) by reacting a compound of formula (I) wherein s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 138., A is a radical of     (IIa), (IIc) or (IIt) wherein R₂, R_(a), R_(c), d, d′ and R_(t) are     as defined in 138., R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   138b) by reacting a compound of formula A with a compound of formula     (IIIe)     A+Act(O)C—Y—ONO₂  (IIIe)     wherein Act and Y are as above defined and A is a radical of (IIa),     (IIc) or (IIt) wherein R₁ is —C(O)OC(CH₃)₃; R₂ is equal to R₄; R_(a)     of formula (IIa) and R_(c) of formula (IIc) are R_(h)NH(CH₂)_(p)—     wherein p is an integer from 0 to 4, or R_(i)NH(═NH)NH—(CH₂)₃—,     wherein R_(h) and R_(i) are —H; -   in formula (IIt) d and d′ are as defined in 138., R_(t) is —H;     using the same procedure described in 1b′). -   138c) by reacting a compound of formula A with a compound of formula     (IIIx) or (IIIy)     A+(IIIx)     A+(IIIy)     wherein A is a radical of formula (IIa), (IIc) or (IIt) wherein R₁     is —C(O)OC(CH₃)₃; R₂ is —COOH or R_(2a) wherein R_(2a) is the group     —COAct as already described in 8; R_(a) of formula (IIa) and R_(c)     of formula (IIc) are R_(h)NH(CH₂)_(p)— wherein p is an integer from     0 to 4, or R_(i)NH(═NH)NH—(CH₂)₃—, wherein R_(h) and R_(i) are —H; -   in formula (IIt) d and d′ are as defined in 138., R_(t) is —H;     using the same procedures described in 114b). -   130. The compounds of general formula (I) wherein: -   s is equal to 1; -   s′, s″, m, m′ and m″ are equal to 0; -   Y is as above defined; -   A is selected from (IIa), (IIc) and (IIt) wherein R₁ is —H; R₂ is     equal to R₄ and is as defined in 114., -   R_(a) of formula (IIa) and R_(c) of formula (IIc) are     R_(h)NH(CH₂)_(p)— wherein p is an integer from 0 to 4, or     R_(i)NH(═NH)NH—(CH₂)₃—,     wherein R_(h) and R_(i) are R_(hh)—OC(O)— or R_(ii)—OC(O)—; and bind     a group —Y—ONO₂; -   in formula (IIt) d is 2 d′ is 1, R_(t) is —C(O)O—R_(tt), and it     binds a group —Y—ONO₂;     can be obtained as follows: -   139a) by reacting a compound of formula (I) wherein s, s′, s″, m,     m′, m″, Y, Y′, Y″ are as above defined in 139., A is a radical of     (IIa), (IIc) or (IIt) wherein R₂, R_(a), R_(c), d, d′ and R_(t) are     as defined in 139., R₁ is —C(O)OC(CH₃)₃; -   with anhydrous or aqueous organic or inorganic acid to hydrolyze the     —BOC protective groups following procedure well known in the     literature. -   139b) by reacting a compound of formula A described in 138b) with a     compound of formula (IIIf)     A+Act(O)C—O—Y—ONO₂  (IIIf)     wherein Act and Y are as above defined using the same procedure     described in 3b).

EXAMPLE 1

(S)-4-(nitrooxy)butyl 2-amino-6-(tert-butoxycarbonylamino)hexanoate (Corresponding to Compound 18) Step A: (S)-4-(nitrooxy)butyl 1-(9H-fluoren-9-yl)-13,13-dimethyl-3,11-dioxo-2,12-dioxa-4,10-diazatetradecane-5-carboxylate

Commercial N(α)-Fmoc-N(ε)-Boc-L-lysine pentafluorophenyl ester (6.51 mmol) and 4-(nitrooxy)-1-butanol (6.55 mmol) were dissolved in DMF (12 ml) and the mixture was cooled to 0° C. N,N-dimethylaminopyridine (DMAP) (6.55 mmol) were added and the reaction was slowly warmed to room temperature and stirred for 4 hours. Then the mixture was concentrate under reduced pressure and diluted with EtOAc, washed with 5% aqueous Na₂HPO₄ and brine.

The organic layer was dried over sodium sulphate and concentrated under reduced pressure.

The residue was purified by flash chromatography (n-hexan/EtOAc 70:30 as eluent) yielding the title compound (2.52 g, 66%).

Step B: (S)-4-(nitrooxy)butyl 2-amino-6-(tert-butoxycarbonylamino)hexanoate

To a solution of S)-4-(nitrooxy)butyl 1-(9H-fluoren-9-yl)-13,13-dimethyl-3,11-dioxo-2,12-dioxa-4,10-diazatetradecane-5-carboxylate (2.52 g, 4.30 mmol) in CH₃CN (30 ml), piperidine (2.12 ml, 21.5 mmol) was added in the dark, the reaction was stirred at rt for 25 min. Then the mixture was concentrated to a small volume and diluted with EtOAc (150 ml) and washed with 5% aqueous NaHPO₄ (2×70 ml). The organic layer was dried over sodium sulphate and concentrated under reduced pressure.

The residue was purified by flash chromatography (CH₂Cl₂/MeOH 98:2 as eluent), yielding the title compound (0.960 g, 61%).

¹H-NMR (DMSO-d₆): 6.78 (1H, t), 4.55 (2H, t), 4.07 (2H, m), 3.26 (2H, t), 2.87 (1H, m), 1.73-1.65 (4H, m), 1.64-1.40 (2H, m), 1.37 (9H, s), 1.36-1.22 (4H, s).

EXAMPLE 2

2-Amino-3-tert-butoxy-3-oxopropyl 4-(nitrooxy)butanoate (Corresponding to Compound 405) Step A: tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-hydroxypropanoate

To a solution of commercial N-Fmoc-L-serine (1.5 g, 4.58 mmol) in EtOAc (40 ml), a solution of t-butyl 2,2,2-trichloroacetimidate (4.00 g, 18.32 mmol) in cyclohexane (18 ml) was added dropwise. After stirring at room temperature for 24 hrs, the solution was evaporated and the residue was purified by flash chromatography (n-Hexane/EtOAc 70:3), yielding the title compound (1.20 g, 68%).

Step B: 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-tert-butoxy-3-oxopropyl 4-(nitrooxy)butanoate

To a solution of 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-tert-butoxy-3-oxopropyl 4-(nitrooxy)butanoate (1.20 g, 3.13 mmol), 4-(nitrooxy)butyric acid pentafluorophenyl ester (1.18 g, 3.76 mmol) and scandium trifluoromethanesulfonate (0.308 g, 0.626 mmol) in CH₂Cl₂ (25 ml) cooled to 0° C., was added N,N-dimethylaminopyridine (DMAP) (0.459 g, 3.76 mmol). The resulting mixture was stirred at room temperature for 18 hours. Then it was diluted with CH₂Cl₂ and washed with 5% aqueous Na₂HPO₄ and brine. The organic layer was dried over sodium sulphate and concentrated under reduced pressure.

The residue was purified by flash chromatography (n-hexane/EtOAc 70:30 as eluent) affording the title compound (1.26 g, 78%).

Step C: 2-Amino-3-tert-butoxy-3-oxopropyl 4-(nitrooxy)butanoate

To a solution of 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-tert-butoxy-3-oxopropyl 4-(nitrooxy)butanoate 1.26 g, 2.45 mmol) in CH₃CN (15 ml), piperidine (1.21 ml, 12.2 mmol) was added in the dark, the reaction was stirred at room temperature for 25 min. Then the mixture was concentrated to a small volume and diluted with EtOAc (80 ml) and washed with 5% aqueous NaHPO₄. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography (CH₂Cl₂/MeOH 98:2 as eluent) yielding the title compound (0.500 g, 70%).

¹H-NMR (CDCl₃): 6.49, 4.61-4.50 (3H, m), 3.95 (2H, d), 2.43 (2H, t), 2.22-2.08 (2H, m), 1.05 (9H, s).

EXAMPLE 3

1-tert-Butyl 2-(4-(nitrooxymethyl)benzyl)pyrrolidine-1,2-dicarboxylate (Corresponding to Compound 7) Step A: 1-tert-butyl 2-(4-(chloromethyl)benzyl)pyrrolidine-1,2-dicarboxylate

N-Boc-L-prolin (2.47 g, 11.5 mmol) and 4-(chloromethyl)benzyl alcohol (1.50 g, 9.58 mmol) were dissolved in CH₂Cl₂ (50 ml) and the mixture was cooled to 0° C. N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) (2.75 g, 14.4 mmol) and N,N-dimethylaminopyridine (DMAP) (0.235 g, 1.92 mmol) were added and the reaction was slowly warmed to room temperature and stirred for 4 hours. Then the mixture was diluted with CH₂Cl₂ (200 ml) and washed with 5% aqueous NaHCO₃, 5% aqueous Na₂HPO₄ and brine. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography (n-hexane/EtOAc 80:20 as eluent) affording the title compound. (2.98 g, 88%).

Step B: 1-tert-Butyl 2-(4-(nitrooxymethyl)benzyl)pyrrolidine-1,2-dicarboxylate

To a solution of 1-tert-butyl 2-(4-(chloromethyl)benzyl)pyrrolidine-1,2-dicarboxylate (0.630 g, 1.78 mmol) in CH₃CN (13 ml), AgNO₃ (0.756 g, 4.45 mmol) was added and the reaction was heated in a microwave apparatus (150° C., 20 min). The formed salts were filtered off and the solvent was concentrated, then the residue was diluted with EtOAc (100 ml) and washed with brine. The organic layer was dried over sodium sulphate and concentrated under reduced pressure yielding the title compound (0.655 g, 96%).

¹H-NMR (CDCl₃): 7.41 (4H, d), 5.44 (2H, s), 5.30-5.10 (2H, m), 4.42-4.27 (2H, m), 3.57-3.42 (2H, m), 2.30-2.15 (1H, m), 2.00-1.85 (3H, m), 1.48-1.35 (9H, m).

EXAMPLE 4

4-[(nitrooxy)methyl]benzylpyrrolidine-2-carboxylate hydrochloride (Corresponding to Compound 3)

To a solution of 1-tert-Butyl 2-(4-(nitrooxymethyl)benzyl)pyrrolidine-1,2-dicarboxylate, obtained in Example 3, (0.543 g, 1.43 mmol) in CH₂Cl₂ (14 ml) cooled to 0° C., HCl_(gas) was bubbled for 2 hours. The solvent was concentrated and the residue was treated with diethyl ether, affording the title compound (0.446 g, 99%.

¹H-NMR (CDCl₃): 9.16 (bs), 7.40 (4H, d), 5.43 (2H, s) 5.31-5.17 (2H, m), 4.52 (1H, m), 3.52 (2H, m), 2.49-2.38 (1H, m), 2.20-2.00 (3H, m).

EXAMPLE 5

4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)acetate (Corresponding to Compound 16)

Applying the same procedure described in Example 1, starting from commercially available N-Boc-L-glycine, N-hydroxysuccinimido ester (2.33 g, 8.56 mmol), the title compound was obtained. (3.00 g, 80%).

¹H-NMR (CDCl₃) 5.04 (1H, bt), 4.49 (2H, t), 4.20 (2H, t), 3.91 (2H, d), 1.81 (4H, m), 1.46 (9H, s).

EXAMPLE 6

4-(nitrooxy)butyl 2-aminoacetate hydrochloride (Corresponding to Compound 21)

The title compound was obtained as a white solid starting from 4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)acetate, prepared as described in Example 5 following the procedure described in Example 4 (2.34 g, quantitative yield).

¹H-NMR (CDCl₃): 4.53 (2H, t), 4.29 (2H, t), 4.04 (2H, d), 3.74 (2H, d), 1.84 (4H, m).

EXAMPLE 7

4-(Nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-methylbutanoate (Corresponding to Compound 149) Step A: 4-chloro 2-(tert-butoxycarbonylamino)-3-methylbutanoate

N-Boc-L-valine (3.48 g, 16.0 mmol), 4-chloro-1-butanol (3.47 g, 32.0 mmol) and N-hydroxybenzotriazole (HOBT) (3.24 g, 24.0 mmol) were dissolved in CH₂Cl₂ (80 ml) and the mixture was cooled to 0° C. N-Methylmorpholine (NMM) (3.24 g, 32.0 mmol) and N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) (6.67 g, 17.6 mmol) were added and the reaction was slowly warmed to room temperature and stirred for 24 hours. Then the mixture was diluted with CH₂Cl₂ (200 ml) and washed with 5% aqueous NaHCO₃, HCl 1N and brine. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography (n-hexane/EtOAc 90:10) affording the title compound (2.98 g, 64%).

Step B: 4-(Nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-methylbutanoate methylbutanoate

To a solution of 4-chlorobutyl 2-tert-butoxycarbonylamino)-3-methylbutanoate (0.630 g, 1.78 mmol) in CH₃CN (13 ml), AgNO₃ (0.756 g, 4.45 mmol) was added and the reaction was heated in a microwave apparatus (150° C., 20 min). The formed salts were filtered off and the solvent was concentrated. Then the residue was diluted with EtOAc (100 ml) and washed with brine, dried over sodium sulphate and concentrated under reduced pressure yielding the title compound (0.655 g).

¹H-NMR (CDCl₃): 5.00 (1H, d), 4.50 (2H, t), 4.24-4.16 (3H, m), 2.20-2.09 (1H, m), 1.90-1.74 (4H, m), 1.46 (9H, s), 0.99 (3H, d), 0.92 (3H, d).

EXAMPLE 8

tert-butyl 2-(4-(nitrooxy)butylamino)-2-oxoethylcarbamate (Corresponding to Compound (12)) Step A: tert-butyl 2-(4-hydroxybutylamino)-2-oxoethylcarbamate

4-Amino-1-butanol (0.686 g, 7.70 mmol) and triethylamine (0.779 g, 7.70 mmol) were dissolved in CH₂Cl₂ (40 ml) and the mixture was cooled to 0° C. A suspension of commercial N-Boc-glycine N-hydroxysuccinimido ester (2.10 g; 7.70 mmol) in CH₂Cl₂ (40 ml) was added and the reaction was slowly warmed to room temperature and stirred for 24 hours. Then, the mixture was diluted with CH₂Cl₂ (150 ml) and washed with 5% aqueous Na₂HPO₄ and brine. The aqueous layer was extracted twice with CH₂Cl₂ and twice with a mixture of EtOAc/MeOH 98:2. The organic layers were dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography (n-hexane/i-prOH 80:20 affording the title compound (2.16 g).

Step B: 2-(4-(nitrooxy)butylamino)-2-oxoethylcarbamate

To a solution of tert-butyl 2-(4-hydroxybutylamino)-2-oxoethylcarbamate (2.16 g, 8.77 mmol), tetraethylammonium nitrate (3.37 g, 17.54 mmol) and 2,6-di-tert-butyl-4-methylpyridine (2.71 g, 13.16 mmol) in CH₂Cl₂ (60 ml) cooled to −70° C. and under nitrogen, a solution of trifluoromethansulfonic anhydride (2.72 g, 9.65 mmol) in CH₂Cl₂ (40 ml) was added drop wise. The resulting mixture was stirred for 3 hours at −65° C. Then the mixture was slowly warmed to room temperature, diluted with CH₂Cl₂ and washed with 5% aqueous Na₂HPO₄. The organic layer was dried over sodium sulphate and concentrated under reduced pressure.

The residue was purified by flash chromatography CH₂Cl₂/CH₃CN 70:30 as eluent) affording the title compound. (2.04 g, 80%).

¹H-NMR (CDCl₃) 6.30 (1H, s), 5.15 (1H, s), 4.48 (2H, t), 3.79 (2H, d), 3.37-3.31 (2H, m), 1.80-1.74 (2H, m), 1.67-1.62 (2H, m), 1.63 (9H, s).

EXAMPLE 9

4-(2-Aminoacetamido)butyl nitrate hydrochloride (Corresponding to Compound 23)

The title compound was obtained as a white solid from tert-butyl 2-(4-(nitrooxy)butylamino)-2-oxoethylcarbamate (Example 8) following the procedure described in Example 4. (1.58 g, quantitative yield).

¹H-NMR (CDCl₃) 8.55 (1H, s), 8.17 (2H, s), 4.54 (2H, t), 3.55-3.48 (2H, m), 3.18-3.12 (2H, m), 1.72-1.65 (2H, m), 1.53-1.48 (2H, m).

EXAMPLE 10

(2S,3aS,6aS)-4-(Nitrooxy)butyl octahydrocyclopenta[b]pyrrole-2-carboxylate (Corresponding to Compound 512 Step A: (2S,3aS,6aS)-1-(9H-fluoren-9-yl)methyl 2-benzylhexahydrocyclopenta[b]pyrrole-1,2(2H)-dicarboxylate

To a solution of commercial (2S,3aS,6aS)-benzyl octahydrocyclopenta[b]pyrrole-2-carboxylatehydrochloride (1.00 g, 3.60 mmol) and TEA (1.15 ml, 7.92 mmol) in CH₃CN (15 ml) cooled in an ice bath 9-fluorenylmethoxycarbonyl chloride (1.01 g, 4.25 mmol) was added. The resulting mixture was stirred at room temperature overnight. Then the mixture was concentrated and diluted with CH₂Cl₂ (50 ml), washed with a solution of Na₂HPO₄ 5% (2×30 ml) and brine (1×30 ml). The organic phase was dried over sodium sulphate and concentrated under reduced pressure to give an oil that slowly crystallized on storage affording the title compound (1.68 g, 100%).

Step B: (2S,3aS,6aS)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid

To a solution of (2S,3aS,6aS)-1-(9H-fluoren-9-yl)methyl 2-benzylhexahydrocyclopenta[b]pyrrole-1,2(2H)-dicarboxylate (1.68 g, 3.6 mmol) in EtOH 95% (15 ml) was added Palladium on carbon 10% (0.2 g, 0.18 mmol) and cyclohexene (3.5 ml, 36 mmol). The resulting mixture was refluxed for 7 h. The solvent was evaporated and the crude was diluted with CH₂Cl₂ (20 ml). The suspension was filtered on celite the organic phase was evaporated under vacuum. The residue was purified by flash chromatography (CH₂Cl₂/CH₃CN 50:50) to give the title compound as a white foam (0.5 g, 37%)

Step C: (2S,3aS,6aS)-(9H-fluoren-9-yl)methyl 2-(4-chlorobutyl) hexahydrocyclopenta[b]pyrrole-1,2(2H)-dicarboxylate

(2S,3aS,6aS)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid (0.250 g, 0.66 mmol) and 4-chloro-1-butanol (0.1 ml, 0.99 mmol) were dissolved under nitrogen in CH₂Cl₂ (5 ml) and the mixture was cooled to 0° C. N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) (0.190 g, 0.99 mmol) and N,N-dimethylaminopyridine (DMAP) (0.016 g, 0.13 mmol) were added and the reaction was slowly warmed to room temperature and stirred for 4 h. Then the mixture was diluted with CH₂Cl₂ (10 ml) and washed with 5% aqueous NaHCO₃, 5% aqueous Na₂HPO₄ and brine. The organic layer was dried over sodium sulphate, concentrated under reduced pressure and purified by flash chromatography (n-hexane/EtOAc 80:20 as eluent) affording the title compound as an oil (0.14 g, 45%)

Step D: (2S,3aS,6aS)-1-(9H-fluoren-9-yl)methyl 2-(4-(nitrooxy)butyl)hexahydrocyclopenta[b]pyrrole-1,2(2H)-dicarboxylate

To a solution of (2S,3aS,6aS)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid (0.13 g, 0.27 mmol) in CH₃CN (1.7 ml), AgNO₃ (0.118 g, 0.69 mmol) was added and the reaction was heated to 150° C. for 20 min in a microwave apparatus. The formed salts were filtered off and the solvent was concentrated affording the title compound as a yellow solid (0.133 g, 100%).

To a solution of (2S,3aS,6aS)-1-(9H-fluoren-9-yl)methyl 2-(4-(nitrooxy)butyl)hexahydrocyclopenta[b]pyrrole-1,2(2H)-dicarboxylate (0.133 g, 0.27 mmol) in CH₃CN (2 ml), piperidine (133 μl, 1.35 mmol) was added in the dark; the reaction was stirred at room temperature for 25 min. Then the solution was evaporated, diluted with pH 3 aqueous buffer and the aqueous phase was extracted with hexane. The solution was basified to pH 9 and finally extracted with diethyl ether. The organic layer was dried over sodium sulphate and concentrated under reduced pressure affording the title compound as an oil (0.04 g, 50%).

¹H-NMR (DMSO-d₆) 4.55 (2H, t); 4.13-3.96 (3H, m); 3.81 (1H, m); 3.68 (1H, bs); 2.66-2.51 (1H, m); 2.34-2.19 (1H, m); 1.81-1.31 (11H, m).

EXAMPLE 11

(2S,3aS,6aS)-4-(nitrooxymethyl)benzyl octahydrocyclopenta[b]pyrrole-2-carboxylate (Corresponding to Compound 520)

The title compound was prepared following the procedure described in Example 10 using 4-(chloromethyl)benzyl alcohol instead of 4-chloro-1-butanol in Step C.

¹H-NMR (DMSO-d₆): 7.51-7.21 (4H, m); 5.47 (2H, s); 5.09 (2H, s) 4.10 (1H, m); 3.82 (1H, m); 3.68 (1H, m); 2.62 (1H, m); 2.38 (1H, m); 1.92-1.05 (9H, m)

EXAMPLE 12

4-[(nitrooxy)methyl]benzyl 2-amino-6-(tert-butoxycarbonylamino)hexanoate (Corresponding to Compound 24)

The title compound was prepared following procedure already described in Examples 1 and 11 (0.010 g, 10%).

¹H-NMR (DMSO-d₆): 7.48-7.61 (8H, m); 6.78 (1H, t); 5.54 (2H, s); 5.15 (2H, s); 4.07 (1H, m); 2.87 (1H, m); 1.73-1.65 (2H, m); 1.36-1.22 (13H, m).

EXAMPLE 13

4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-hydroxypropanoate (Corresponding to Compound (45))

Starting from Boc-L-serine and following the procedure described in Example 3 the title was obtained as an oil (0.350 g, 48%).

¹H-NMR (CDCl₃): 5.44 (1H, bs); 4.50 (2H, t); 4.38 (1H, m); 4.25 (2H, m); 3.97 (2H, m); 1.84 (4H, m); 1.47 (9H, s).

EXAMPLE 14

1-tert-butyl 2-(4-(nitrooxy)butyl)pyrrolidine-1,2-dicarboxylate

Starting from Boc-L-Proline and 4-chloro-1-butanol and following the procedure described in Example 3 the title compound was obtained as an oil.

¹H-NMR (CDCl₃): 4.50 (2H, t), 4.10-4.40 (3H, m), 3.65-3.33 (2H, m), 2.34-1.70 (8H, m), 1.45 (9H, d).

EXAMPLE 15

1-tert-butyl 2-(3-(nitrooxy)propyl)pyrrolidine-1,2-dicarboxylate

Starting from Boc-L-Proline and 3-bromo-1-propanol and following the procedure described in Example 3 the title compound was obtained as an oil.

¹H-NMR (CDCl₃): 4.56-4.52 (2H, m); 4.31-4.19 (3H, m); 3.57-3.35 (2H, m); 2.28-1.80 (6H, m); 1.43 (9H, d).

EXAMPLE 16

2,2-dimethyl-15-(nitrooxy)-4,9-dioxo-3,8,10,13-tetraoxa-5-azapentadecane-6-carboxylic acid (Corresponding to Compound 400)

Into a solution or N-Boc-L-Serine (1.66 g, 8.12 mmol), diisopropylethyl amine (DIPEA) (1.41 ml, 8.12 mmol), N,N-dimethylaminopyridine (DMAP) (1.19 g, 9.74 mmol) and scandium triflate (1.20 g, 2.43 mmol) in CH₂Cl₂ (40 ml), cooled to −10° C., a solution of 2-[2-(nitrooxy)ethoxy]ethyl 4-nitrophenyl carbonate in CH₂Cl₂ (40 ml) was added drop-wise. The reaction was slowly warmed to room temperature and stirred for 24 h. Then the organic phase was washed with pH 3 aqueous buffer and concentrated under reduced pressure. The crude was partitioned between aqueous 5% aqueous Na₂HPO₄ and diethyl ether and extracted twice with diethyl ether. The aqueous phase was acidified to pH 3 and extracted with CH₂Cl₂. The organic phase was finally dried over sodium sulphate and concentrated under reduced pressure to give the title compound as an oil. (2.4 g, 80%)

¹H-NMR (CDCl₃): 5.54 (1H, bs); 4.63 (2H, m); 4.52 (3H, m); 4.29 (2H, m); 3.86-3.69 (4H, m); 1.46 (9H, s).

EXAMPLE 17

2-(tert-butoxycarbonylamino)-4-methylpentyl 4-hydroxybutanoate (Corresponding to Compound (510)) Step A: 2-(tert-butoxycarbonylamino)-4-methylpentyl 4-bromobutanoate

tert-Butyl 1-hydroxy-4-methylpentan-2-ylcarbamate (2.00 g, 9.20 mmol) and 4-bromo-butyric acid (2.57 g, 15.38 mmol) were dissolved in CH₂Cl₂ (40 ml) and the mixture was cooled to 0° C. EDC (4.20 g, 21.90 mmol) and DMAP (0.27 g, 2.21 mmol) were added and the reaction was slowly warmed to room temperature and stirred overnight. Then the reaction was treated with a solution of 5% aqueous NaH₂PO₄ (100 ml). The organic layer was washed with a solution of 10% aqueous Na₂CO₃ (100 ml) and brine, dried over Na₂SO₄, filtered and concentrated. The obtained crude clear oil corresponding to the title compound (3.30 g) was used without any further purification.

Step B: 2-(tert-Butoxycarbonylamino)-4-methylpentyl 4-(nitrooxy)butanoate

To a solution of crude 2-(tert-butoxycarbonylamino)-4-methylpentyl 4-bromobutanoate (3.30 g) in CH₃CN (60 ml), AgNO₃ (4.20 g, 24.52 mmol) was added. The resulting solution (divided into 5 vials) was heated in a microwave apparatus (120° C., 3 minutes). Then the formed salts were filtered off, the solvent was concentrated and the residue purified by flash chromatography (n-hexane/EtOAc 80:20 as eluent) affording the title compound (1.05 g, yield: 33.5%) as a clear oil.

¹H-NMR (CDCl₃): 4.54 (2H, t); 4.48-4.34 (1H, m); 2.49 (2H, t); 2.18-1.99 (2H, m); 1.79-1.57 (1H, m); 1.39-1.22 (2H, m); 1.00-0.86 (6H, m).

EXAMPLE 18

2-Amino-4-methylpentyl 4-(nitrooxy)butanoate hydrochloride (Corresponding to Compound 507)

The title compound was prepared from 2-(tert-butoxycarbonylamino)-4-methylpentyl 4-(nitrooxy)butanoate (described in Example 17) following the procedure described in Example 4 (0.71 g, 90%).

¹H-NMR (DMSO-d₆): 4.56 (2H, t); 4.27-4.22 (1H, m); 4.11-4.06 (1H, m); 3.39-3.32 (2H, m); 2.51 (2H, t); 2.01-1.92 (2H, m); 1.75-1.68 (1H, m); 1.51-1.38 (2H, m); 0.90 (6H, d).

EXAMPLE 19

4-[(Nitrooxy)methyl]benzyl 2-(tert-butoxycarbonylamino)-4-phenylbutanoate (Corresponding to Compound 13)

The title compound was prepared as a clear oil from 2-(tert-butoxycarbonylamino)-4-phenylbutanoic acid following procedure described in Example 3.

¹H-NMR (CDCl₃): 7.34 (4H, m); 5.07-5.04 (1H, m); 4.49 (2H, t); 4.36-4.34 (1H, m); 4.23-4.11 (2H, m); 2.70 (2H, t); 2.19-2.11 (1H, m); 2.02-1.94 (1H, m); 1.92-1.76 (4H, m); 1.61 (9H, s).

EXAMPLE 20

3-[(Nitrooxy)methyl]phenyl 2-(tert-butoxycarbonylamino)-4-phenylbutanoate (Corresponding to Compound 86)

Starting from 2-(tert-butoxycarbonylamino)-4-phenylbutanoic acid and 3-(bromomethyl)phenyl alcohol and following the procedure reported in Example 3 the title compound was obtained as an oil.

¹H-NMR (CDCl₃): 7.50-7.16 (7H, m); 7.15-7.05 (2H, m); 5.42 (2H, s); 5.07 (1H, d); 4.65-4.47 (1H, m); 2.80 (2H, t); 2.44-2.23 (1H, m); 2.23-1.99 (1H, m); 1.48 (9H, s).

EXAMPLE 21

2-(2-(Nitrooxy)ethoxy)ethyl 2-(tert-butoxycarbonylamino)-4-phenylbutanoate

Starting from 2-(tert-butoxycarbonylamino)-4-phenylbutanoic acid and 2-chloroethoxyethyl alcohol and following the procedure reported in Example 3 the title compound was obtained as an oil.

¹H-NMR (CDCl₃): 7.19-7.03 (5H, m); 5.08 (1H, d); 4.50-4.45 (2H, m); 4.22-4.06 (3H, m); 3.65-3.55 (4H, m); 2.56 (2H, t); 2.08-1.80 (2H, m); 1.32 (9H, s).

EXAMPLE 22

2,2-Dimethyl-14-(nitrooxy)-4,9-dioxo-3,8,10-trioxa-5-azatetradecane-6-carboxylic acid (Corresponding to Compound (401))

The title compound was prepared from N-Boc-L-serine and 4-chlorobutyl chloroformate following procedure described in Example 16.

¹H-NMR (CDCl₃): 5.50 (1H, d); 4.52-4.40 (5H, m); 4.19 (2H, t); 1.88-1.75 (4H, m); 1.46 (9H, s).

EXAMPLE 23

2-amino-3-((4-(nitrooxy)butoxy)carbonyloxy)propanoic acid hydrochloride (Corresponding to Compound (407))

The title compound was obtained as a white solid from 2,2-dimethyl-14-(nitrooxy)-4,9-dioxo-3,8,10-trioxa-5-azatetradecane-6-carboxylic acid (described in Example 22) following procedure described in Example 4.

¹H-NMR (DMSO-d₆): 4.60-4.41 (4H, m); 4.18-4.13 (3H, m); 1.78-1.65 (4H, m).

EXAMPLE 24

4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propanoate (Corresponding to Compound 67)

To a solution of Boc-(L)-tyrosine 5.0 g, 17.77 mmol) in N,N-dimethylformamide (40 ml) cesium carbonate (5.79 g, 17.77 mmol) was added. The reaction was cooled at 0° C. and a solution or 4-bromobutyl nitrate (17.77 mmol) in dichloromethane (20% w/w, 17.06 g) was added drop wise. The reaction was stirred at 0° C. for 20 minutes and then at room temperature for 22 hours. The mixture was poured into a 5% aqueous NaH₂PO₄ solution and extracted with diethyl ether (40×4 ml), the organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (n-hexane/EtOAc from 9:1 to 1:1 as eluent affording the title compound.

¹H-NMR (CDCl₃): 7.00 (2H, d, J=8 Hz); 6.76 (2H, d, J=8 Hz); 5.01 (1H, bd, J=8 Hz); 4.51 (1H, m); 4.42 (2H, t, J=6 Hz); 4.12 (2H, m); 3.00 (2H, d, J=6 Hz); 1.69 (4H, m); 1.44 (9H, s).

EXAMPLE 25

4-(nitrooxy)butyl 2-amino-3-(4-hydroxyphenyl)propanoate (Corresponding to Compound (58)

The title compound was obtained from 4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propanoate (described in Example 24) following procedure described in Example 4.

¹H-NMR (CDCl₃): 7.05 (2H, dd, J=9 and 3 Hz); 6.74 (2H, dd, J=9 and 3 Hz); 4.45 (2H, t, J=6 Hz); 4.15 (2H, t, J=6 Hz); 3.73 (1H, m); 2.93 (2H, m); 1.73 (4H, m).

EXAMPLE 26

2-(R)-5,6-bis(nitrooxy)hexyl 1-tert-butyl pyrrolidine-1,2-dicarboyxlate (Corresponding to Compound 4, 5-(R)-isomer)

To a solution of N-Boc-L-Proline (288 mg, 1.34 mmol) and (2R)-6-hydroxypentane-1,2-diyl dinitrate (obtained as described in WO2005070868(A1)) (300 mg, 1.34 mmol) in CH₂Cl₂ (6 ml) was added at 0° C. EDAC (257 mg, 1.34 mmol), and then DMAP (catalytic). The reaction was stirred overnight at rt. The organic layer was washed successively with H₂O, HCl 0.1M, H₂O and brine, dried over Na₂SO₄, filtered and evaporated. The residue was purified by column chromatography on silica (15% to 25% AcOEt in n-Hexane in 20 CV then 25% to 35% in 5 CV) to give the title compound (413 mg, 73%).

¹H-NMR (300 MHz, CDCl₃) δ 5.30 (m, 1H), 4.77 (m, 1H), 4.50 (m, 1H), 4.31 (d, J=11.5 Hz, 1H), 4.19 (m, 2H), 3.47 (m, 2H), 1.94 (m, 3H), 1.76 (m, 4H), 1.56 (m, 3H), 1.45 (d, J=12.67 Hz, 9H).

EXAMPLE 27

(R)-5,6-bis(nitrooxy)hexylpyrrolidine-2-carboxylate (Corresponding to Compound 1; 5(R)-isomer)

To a solution of [(5R)-5,6-dinitroxyloxane-1-yl]N-tButoxy-L-proline ester (410 mg, 0.97 mmol) in CH₂Cl₂ (3 mL) was added TFA (223 μL, 2.91 mmol, 3 eq). The reaction was stirred at RT for 3 hrs. The organic layer was washed with H₂O, K₂CO₃ diluted, H₂O and brine, dried over Na₂SO₄, filtered and evaporated yielding the title compound (215 mg, 69%).

¹H-NMR (300 MHz, CDCl₃) δ 5.31 (ddd, J=13.23, 6.51, 3.09 Hz, 1H), 4.77 (dd, J=12.88, 3.07 Hz, 1H), 4.50 (dd, J=12.87, 6.46 Hz, 1H), 4.17 (t, J=6.30 Hz, 2H), 3.82 (dd, J=8.46, 5.25 Hz, 1H), 3.13 (dd, J=16.88, 6.54 Hz, 1H), 2.42 (s, 2H), 2.17 (m, 1H), 1.78 (m, 6H), 1.52 (m, 3H).

EXAMPLE 28

2-(tert-butoxycarbonylamino)ethyl 4-(nitrooxy)butanoate (Corresponding to Compound (508)) Step A: 2-(tert-butoxycarbonylamino)ethyl 4-bromobutanoate

N-Boc-ethanolamine (2.10 g; 13.0 mmol), 4-Bromobutyric acid (2.18 g; 13.0 mmol) and N,N-dimethylaminopyridine (0.318 g; 2.60 mmol) were dissolved in CH₂Cl₂ (35 mL) and the mixture was cooled to 0° C.; EDAC (3.75 g; 13.6 mmol) was added and the reaction was slowly warmed to room temperature and stirred for 18 hours. Then the mixture was diluted with CH₂Cl₂, washed with aqueous Na₂HPO₄ (5%, 2×50 ml) aqueous NaH₂PO₄, (5%, 2×50 ml) and brine (1×40 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure.

The residue was purified by flash chromatography (hexane/EtOAc=75/25; R_(f)=40), yielding the title compound (3.03 g, 75%).

Step B: 2-(tert-butoxycarbonylamino)ethyl 4-(nitrooxy)butanoate

To a solution of 2-(tert-butoxycarbonylamino)ethyl 4-bromobutanoate (3.03 g; 9.77 mmol) in CH₃CN (80 mL), AgNO₃ (4.15 g; 24.4 mmol) was added and the reaction was performed at the microwave (120° C., 7 min). The formed salts were filtered off and the solvent was concentrated; then the residue was diluted with EtOAc and washed with water (40 ml); the organic layer was dried over sodium sulfate and concentrated under reduced pressure.

The residue was purified by flash chromatography (hexane/EtOAc=7/3; R_(f)=0.40), yielding the title compound (1.48 g, 52%).

¹H-NMR (300 MHz, CDCl₃): 4.77 (1H, s); 4.54 (2H, t); 4.17 (2H, t); 3.44-3.38 (2H, m); 2.49 (2H, t); 2.13-2.04 (2H, m); 1.46 (9H, s).

EXAMPLE 29

2-aminoethyl 4-(nitrooxy)butanoate hydrochloride (Corresponding to Compound (509))

The title compound was obtained as a white solid starting from 2-(tert-butoxycarbonylamino)ethyl 4-(nitrooxy) butanoate, prepared, as described in Example 28 following the procedure described in Example 4 (1.16 g; quantitative yield).

¹H-NMR (DMSO-d₆): 8.25 (2H, s); 4.56 (2H, t); 4.23 (2H, t); 3.06 (2H, t); 2.51 (2H, t); 2.01-1.91 (2H, m).

EXAMPLE 30

(S)-2-(tert-butoxycarbonylamino)-3-phenylpropyl 4-(nitrooxy)butanoate (Corresponding to Compound (511))

The title compound was prepared from (S)-tert-butyl 1-hydroxy-3-phenylpropan-2-ylcarbamate and 4-Bromobutyric acid following the procedure described in Example 29.

¹H-NMR (300 MHz, CDCl₃): 7.35-7.25 (5H, m); 4.56-4.54 (1H, m); 4.52 (2H, t); 4.15-4.04 (3H, m); 2.84-2.81 (2H, m); 2.50 (2H, t); 2.13-2.04 (2H, m); 1.32 (9H, s).

EXAMPLE 31

(S)-4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-phenylpropanoate (Corresponding to Compound (15))

The title compound was prepared from (S)-2-(tert-butoxycarbonylamino)-5-phenylpropanoic acid and 4-chloro-1-butanol following the procedure described in Example 3.

¹H-NMR (300 MHz, CDCl₃): 7.31 (3H, m), 7.16 (2H, d), 4.98 (1H, bd), 4.56 (1H, bm), 4.41 (2H, t), 4.12 (2H, m), 3.08 (2H, d), 1.69 (4H, m), 1.93 (9H, s).

EXAMPLE 32

(S)-4-hydroxybutyl pyrrolidine-2-carboxylate

The title compound was prepared from Boc-Proline and 4-chloro-1-butanol following the procedure described in Example 3, eventually hydrolyzing the Boc protective group as described in Example 4.

¹H-NMR (CDCl₃): 4.5 (3H, m), 4.3 (2H, bt), 3.57 (2H, m), 2.45 (1H, m) 2.13 (3H, m), 1.87 (4H, m).

EXAMPLE 33

((S)-bis(4-nitrooxy)butyl) 2-(tert-butoxycarbonylamino)succinate (Corresponding to Compound (468))

The title compound was prepared from L-Boc-Aspartic acid and 4-chloro-1-butanol following the procedure described in Example 3.

¹H-NMR (CDCl₃): 5.48 (1H, bd), 4.58 (1H, bd), 4.51 (4H, t), 4.23 (2H, t), 2.93 (2H, m), 1.81 (8H, m), 1.47 (9H, s).

EXAMPLE 34

(S)—((R)-5,6-bis(nitrooxy)hexyl) 2-(tert)-butoxycarbonylamino)-3-phenylpropanoate (Corresponding to Compound (123, 5(R)-isomer))

The title compound was prepared from Boc-L-Phenylalanine and (2R)-6-hydroxypentane-1,2-diyl dinitrate (obtained as described in WO2005070868(A1)) following the procedure described in Example 26.

EXAMPLE 35

(S)—((R)-5,6-bis(nitrooxy)hexyl) 2-amino-3-phenylpropanoate (Corresponding to Compound 14 5(R)-isomer)

The title compound was prepared from (S)—((R)-5,6-bis)nitrooxy)hexyl) 2-(tert-butoxycarbonylamino)-3-phenylpropanoate (prepared as described in Example 34) following procedure described in Example 4.

¹H-NMR (CDCl₃): 9.04-8.65 (2H, m), 7.47-7.14 (5H, m), 5.31-5.15 (1H, m), 4.80-4.65 (1H, m), 4.55-4.31 (1H, m), 4.23-3.96 (2H, m); 3.60-3.42 (1H, m); 3.42-3.23 (1H, m); 1.74-1.46 (4H, m); 1.45-1.15 (2H, m).

EXAMPLE 35

4-[(nitrooxy)methyl]benzyl 2-(tert-butoxycarbonylamino)acetate (Corresponding to Compound (87))

The title compound was prepared from N-Boc-Glycine N-hydroxysuccinimido ester and 4-(chloromethyl)benzyl alcohol following procedures reported in Example 3.

¹H-NMR (CDCl₃): 7.41 (4H, s), 5.44 (2H, s), 5.19 (2H, s), 5.02 (1H, bs), 3.97 (2H, d), 1.47 (9H, s).

EXAMPLE 36

4-[(nitrooxy)methyl]benzyl 2-aminoacetate (Corresponding to Compound (33))

The title compound was prepared from 4-[(nitrooxy)methyl]benzyl 2-(tert-butoxycarbonylamino)acetate (prepared in Example 35) following procedures reported in Example 4.

¹H-NMR (CDCl₃): 8.66-8.34 (2H, m), 7.59-7.40 (4H, m), 5.59 (2H, s), 5.26 (2H, s), 3.87 (2H, s).

EXAMPLE 37

(S)-bis(4-nitrooxy)butyl) 2-(tert-butoxycarbonylamino)pentanedioate (Corresponding to Compound (87)) (472))

The title compound was prepared from L-Boc-Glutamic acid and 4-chloro-1-butanol following procedure described in Example 3, eventually hydrolyzing the Boc protective group as described in Example 4.

¹H-NMR (CDCl₃): 5.28 (1H, bd), 4.48 (1H, bd), 4.19 (2H, t), 4.07 (2H, t), 2.40 (3H, m), 2.03 (1H, m), 1.72 (8H, m), 1.45 (9H, s).

EXAMPLE 38

(S)-4-(nitrooxy)butyl 2-amino-3-phenylpropanoate (Corresponding to Compound (40))

The title compound was prepared from (S)-4-(nitrooxy)butyl 2-(tert-butoxycarbonylamino)-3-phenylpropanoate (prepared as described in Example 31) following procedure described in Example 4.

¹H-NMR (DMSO): 8.7 (3H, bs), 7.30 (5H, m), 4.47 (2H, d), 4.25 (1H, t), 4.08 (2H, t), 3.15 (2H, m), 1.54 (4H, m).

PHARMACOLOGICAL EXAMPLE

The ability of the compounds of the present invention to release nitric oxide was assessed testing their vasorelaxant activity in isolated rabbit thoracic aorta preparations (Wanstall J. C. et al., Br. J. Pharmacol., 134:463-472, 2001).

The compounds of the invention that were tested are the compounds of the following formulas: 7, 8, 9, 12, 13, 15, 86, 87, 123, 407, 508, 511;

and compounds reported in Examples 14, 15, and 21.

Method

Male New Zealand rabbits were anaesthetized with thiopental-Na (50 mg/kg, iv), sacrificed by exsanguinations and then the thorax was opened and the aorta dissected. Single ring preparations (4 mm in length) of thoracic aorta were set up in physiological salt solution (PSS) at 37° C. in small organ chambers (5 ml). The composition of PSS was (mM): NaCl 130, NaHCO₃ 14.9, KH₂PO₄ 1.2, MgSO₄ 1.2, HEPES 10, CaCl₂, ascorbic acid 170 and glucose 1.1 (95%)₂/5% CO₂; pH 7.4). Each ring was mounted under 2 g passive tension in 5 ml organ bath. Isometric tension was recorded with a Grass transducer (Grass FT03) attached to a BIOPAC MP150 System. Preparations were allowed to equilibrate for 1 h, then contracted submaximally with noradrenaline (NA, 1 μM) and, when the contraction was stable, acetylcholine (ACh, 10 μM) was added. A relaxant response to ACh indicated the presence of a functional endothelium. When a stable precontraction was reached, a cumulative concentration-response curve to either of the vasorelaxant agents was obtained in the presence of a functional endothelium. Time intervals between different concentrations were based on the time needed to reach a full response.

Moreover, the nitric oxide-dependent vascular relaxation elicited by the tested compounds was examined preincubating the aortic rings with the soluble guanylyl cyclase inhibitor ODQ (1H-(1,2,4)-oxadiazol(4,3-a)quinoxalin-1-one) at 10 μM for 20 min. Responses to vasorelaxing agents were measured from the plateau of NA contraction. The IC₅₀ (concentration giving 50% reversal of NA contraction) was interpolated from the plots of relaxant-response vs log molar concentration of tested compound.

During the experimental period, the plateau obtained with NA was stable without significant spontaneous loss of contraction in the aortic rings.

As shown in the following Table 1, the compounds of the invention were able to induce relaxation in a concentration-dependent manner. Furthermore, in experiments performed in the presence of ODQ (10 μM), the vascular relaxation of the tested compounds was inhibited.

TABLE 1 Compound IC₅₀ (μM) ± sem Example 15  1.2 ± 0.33 Example 14 1.9 ± 0.4 Compound 8 2.6 ± 0.6 Compound 7 2.4 ± 0.5 Compound 9 4.5 ± 1.4 Compound 86 5.2 ± 0.9 Compound 13 10.2 ± 0.5  Example 21 8.0 ± 1.8 Compound 87 2.1 ± 0.4 Compound 12 10.2 ± 4.2  Compound 508 4.4 ± 0.7 Compound 15 12.6 ± 6.4  Compound 511 9.5 ± 3.6 Compound 123 0.64 ± 0.14 Compound 407 16 ± 6.4 IC₅₀ is the concentration which inhibits 50% of the response. 

The invention claimed is:
 1. A compound and pharmaceutically acceptable salts or stereoisomers thereof selected from the group consisting of:


2. A medicament comprising a compound according to claim 1 and one or more pharmaceutically acceptable excipients.
 3. A pharmaceutical composition comprising a compound according to claim 1 and one or more pharmaceutically acceptable excipients.
 4. A composition comprising at least a compound of formula (I) according to claim 1 and at least one therapeutic agent selected from the group consisting of: anti-inflammatory drugs, drugs used to treat cardiovascular diseases, drugs for treating ocular diseases, and drugs for treating respiratory disorders.
 5. A medicament comprising the composition according to claim 4 and one or more pharmaceutically acceptable excipients.
 6. The composition according to claim 4 wherein the compound and the at least one therapeutic agent are administered simultaneously or sequentially.
 7. A pharmaceutical composition comprising the composition according to claim 4 and one or more pharmaceutically acceptable excipients.
 8. A method for treating a condition comprising administering a compound according to claim 1, wherein the condition is selected from the group consisting of cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases including glaucoma, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolism dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, inhibition of platelet aggregation and platelet adhesion, pathological conditions resulting from abnormal cell proliferation and vascular diseases.
 9. A method for treating a condition comprising administering the composition according to claim 4, wherein the condition is selected from the group consisting of cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases including glaucoma, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metabolism dysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, inhibition of platelet aggregation and platelet adhesion, pathological conditions resulting from abnormal cell proliferation and vascular diseases. 